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Hindawi Publishing CorporationJournal of CatalystsVolume 2013 Article ID 893512 14 pageshttpdxdoiorg1011552013893512

Review ArticleSchiff Bases A Versatile Pharmacophore

Anu Kajal Suman Bala Sunil Kamboj Neha Sharma and Vipin Saini

M M College of Pharmacy Maharishi Markandeshwar University Mullana Ambala Haryana 133207 India

Correspondence should be addressed to Suman Bala sumankmj7gmailcom

Received 3 March 2013 Revised 19 June 2013 Accepted 28 June 2013

Academic Editor Adel A Ismail

Copyright copy 2013 Anu Kajal et al This is an open access article distributed under the Creative Commons Attribution Licensewhich permits unrestricted use distribution and reproduction in any medium provided the original work is properly cited

Schiff bases are condensation products of primary amines with carbonyl compounds gaining importance day by day in presentscenario Schiff bases are the compounds carrying imine or azomethine (ndashC=Nndash) functional group and are found to be aversatile pharmacophore for design and development of various bioactive lead compounds Schiff bases exhibit useful biologicalactivities such anti-inflammatory analgesic antimicrobial anticonvulsant antitubercular anticancer antioxidant anthelminticantiglycation and antidepressant activities Schiff bases are also used as catalysts pigments and dyes intermediates in organicsynthesis polymer stabilizers and corrosion inhibitors The present review summarizes information on the diverse biologicalactivities and also highlights the recently synthesized numerous Schiff bases as potential bioactive core

1 Introduction

Schiff bases are the compounds carrying imine or azome-thine (ndashC=Nndash) functional groupThese are the condensationproducts of primary amines with carbonyl compounds andwere first reported by Hugo Schiff [1ndash3] Schiff bases form animportant class of the most widely used organic compoundsand have a wide variety of applications in many fields includ-ing analytical biological and inorganic chemistry Schiffbases have gained importance in medicinal and pharmaceu-tical fields due to a broad spectrum of biological activitieslike anti-inflammatory [4ndash7] analgesic [5ndash8] antimicrobial[9 10] anticonvulsant [11] antitubercular [12] anticancer[13 14] antioxidant [15] anthelmintic [16] and so forthThe nitrogen atom of azomethine may be involved in theformation of a hydrogen bond with the active centers of cellconstituents and interferes in normal cell processes [17 18]Apart from biological activities Schiff bases are also used ascatalysts intermediates in organic synthesis dyes pigmentspolymer stabilizers [3] and corrosion inhibitors [19] Studiesenlightened that metal complexes show greater biologicalactivity than free organic compounds [20] Augmentationof biological activity was reported by implementation oftransition metals into Schiff bases [21] Schiff bases played aninfluencing role in development of coordination chemistryand were involved as key point in the development of

inorganic biochemistry and optical materials [22] Schiffbases have been utilized as synthons in the preparation ofa number of industrial and biologically active compoundslike formazans 4-thiazolidinines benzoxazines and so forthvia ring closure cycloaddition and replacement reactions[23] Schiff base derivatives in various processes promotedthe researchers for designing of novel heterocyclicaryl Schiffbases for development of new environmental-friendly tech-nology [24]

2 Biological Activities

21 Antimicrobial Activity A series of some novel 5-substi-tuted Schiff and Mannich bases of isatin derivativesthat is 7-(4-((3-(4-(substituted benzylideneamino) phenyl-imino)-5-fluoro-2-oxindolin-1-yl)methyl)piperazin-1-yl)-1-cyclopropyl-6-fluoro-4-oxo-14-dihydroquinoline-3-carbox-ylic acid 1(andashl) (Figure 1) were synthesized and char-acterized for in vitro antibacterial activity Antimicrobialactivity of synthesized compounds was assessed byminimuminhibitory concentration (MIC) in comparison with standardantimicrobial drugs that is ciprofloxacin and ketoconazoleCompound 1c was reported to be more active than both ofthe standard drugs against tested microorganisms whichproves the significance of substituted electron-donatinggroups in improving the antimicrobial activity [25]

2 Journal of Catalysts

N

F

O

N

NN

N CH

Ar Ar Ar

F

N

COOHO

abcdef

ghijkl

1

1 1-C6H5

-4Cl-C6H4

-4OH-C6H4

-4OCH3-C6H4

-4NO2-C6H4

-6OH-C6H4

-4CH3-C6H4

-5NO2-C6H4

-4N(CH3)2-C6H4

-CH=HC-C6H4

-345(OCH3)3-C6H4

-4OH 5-OCH3-C6H4

Figure 1

CH

N NN

HN

Cl

Cl

OBr

R Ra gb hc

id

jekf

R2-NO2

3-NO2

2-OH4-OH2-Cl4-Cl

2

2 24-OCH3

4-N(CH3)2

345-(OCH3)3

2-OH 4-OCH3

2-OH 4-N(C2H5)2

Figure 2

A novel series of Schiff bases that is 6-bromo-2-[2-(26-dichlorophenyl)amino]benzyl-3-(substituted benzyl-ideneamino)-quinazolin-4(3H)-one 2(andashk) (Figure 2) hasbeen synthesized and subjected to antimicrobial activity [26]

Evaluation was carried out for the in vitro antimicrobialactivity by cup platemethod For this S aureus P aeruginosaB subtilis and C albicans were employed Penicillin Gand amphotericin B were taken as standard drugs Resultsrevealed that all compounds have moderate to poor antifun-gal activity and good antibacterial activity [26]

A novel series of pyrazole-based Schiff bases 3(andashj)(Figure 3) 4-[(3-substituted-1H-pyrazol-3-yl)methyleneam-ino]-5-substituted-4H-124-triazole-3-thiols was synthe-sized and screened for antibacterial activity against themicrobial strains of S aureus P aeruginosa B subtilis and Ecoli From the results compound 3f was found to be equallyas active as standard drug ceftriaxone against P aeruginosaB subtilis and E coli and most active against S aureus [27]

Synthesis of new open (4ndash6) (Figures 4ndash6) and macro-cyclic (7) (Figure 7) Schiff bases has been done and evaluatedfor the antimicrobial activity Open Schiff bases were synthe-sized by the condensation of salicylaldehyde and o-vanillinwith 441015840-diaminodiphenylmethane 441015840-diamino diphenylsulphide and diethyl ester of terephthalic acid respectively

Macrocyclic Schiff bases were reported as the con-densation product of 16-bis(2-formylphenyl)hexane with

thiocarbohydrazide In order to test the biological activityof the synthesized compounds four microorganisms (Kpneumoniae E coli S aureus and S typhimurium) wereemployed All the synthesized compounds were found to bemoderate to strongly active [28]

A few novel solid complexes 8 (Figure 8) of La(III)Ce(III) Pr(III) Nd(III) Sm(III) and Gd(III) with Schiffbase that is 9 (Figure 9) 4-hydroxy-3-(1-2-(2-hydroxy-benzylidene)-amino-phenylimino-ethyl)-6-methyl-pyran-2-ones were synthesized and screened for the antibacterialactivity against S aureus E coli and Bacillus species andantifungal activity against A niger Trichoderma andF oxysporum Results revealed that the complexes werebiologically active and have exhibited enhanced antimicro-bial activity than the free ligand (Schiff base) [29]

Some novel Schiff bases macrocyclic tetradentate nitro-gen donor (N

4) 671415-tetrahydroxy-14912-tetraazacyclo-

hexadecane-581316-tetrone ligand-based metal complexes11 (Figure 11) from 10 (Figure 10) were synthesized andscreened for the in vitro antifungal activity and toxicitystudies Minimum inhibitory concentration (MIC) alongwith ergosterol composition assay against C albicans (ATCC10261) C glabrata (ATCC 90030) and C tropicalis (ATCC750) was performed The antimicrobial results indicated thatall the synthesized compoundswere found to be active againstall fungal strains It was observed that Ni(II) complex and

Journal of Catalysts 3

N

N

N

R SH

N

NH

N

R Ra f HH

b g H

c h H

d i H

e j3

3 3

R1

R1 R1

-C2H5

-C2H5

-C2H5

-C2H5

-C2H5

4-OCH3

4-F

4-Cl

H

4-OCH3

4-F

4-F

4-Cl

-C3H724-Cl2

Figure 3

OH

CHN

C

N

HC

HO

H2

4

Figure 4

OH

CH

N

S

N

HC

HO5

Figure 5

OH

HCN

HN C

O

C

O

NH

NCH

HO

OCH3 H3CO

6

Figure 6

CHN

HN

S

N NCH HC

O O

7

Figure 7

O OM

O

N NO

8

H2O

CH3

OH2

NO3

H3C

H3C

M = La(III) Ce(III) Pr(III) Nd(III) and Sm(III)

Figure 8

Co(II) complex drastically reduced ergosterol content of cellmembrane followed by the Cu(II) complex and the liganditself [30]

22 Antidyslipidemic Activity A series of novel keto-enamineSchiff bases 12(andashh) (Figure 12) derived from 8-hydroxy-quinoline was synthesized and subjected for in vitro antiox-idant in vivo antidyslipidemic and postheparin lipolyticactivity


O OH

O N NH

HO

9

H3C

H3C

Figure 9

NH HN

NH HN

HO

HO

OH

OH

O

O O

O

10

Figure 10

Compound 12d which was formed from nucleophilicsubstitutions of 7-methyl aminomethylene-8-oxo-78-dihy-droquinoline-5-carbaldehyde with p-toluidine was found tobe the most potent antidyslipidemic agent [31]

A novel series of keto-enamine Schiff bases 13(andashh)(Figure 13) derived from benzocoumarin was synthesizedfrom 7-hydroxy-4-methyl-2-oxo-2H-benzo [H] chromene-810-dicarbaldehyde

The compounds were evaluated in vitro for their antiox-idant and in vivo for their antidyslipidemic activity TritonWR-1339 was employed to induce hyperlipidemiaThe resultsrevealed that the compounds 13a 13e and 13i displayedsignificant lowering of total cholesterol phospholipids andtriglycerides in the plasma Gemfibrozil was used as astandard to compare the results [32]

23 Anthelmintic Activity A series of new Schiff bases 14(andashe) (Figure 14) containing 4(3H)-quinazoline ring system wassynthesized by the condensation reaction of 3-amino-2-methyl-4(3H)quinazolinone (AMQ) with different substi-tuted aromatic aldehydes in methanol The compounds werealso evaluated for their anthelmintic antioxidant and antimi-crobial activities Indian adult earthworms (P posthuma)were employed for the anthelmintic activity

Piperazine citrate was used as a reference standardwhile DMSO as a control for comparison Results revealedthat all the synthesized compounds were moderately activeexcept compound 14c which was found to be the mostpotent anthelmintic agent due to presence of chloro groupChloro groupmay improve the conductance of wormmusclemembrane that causes reduction in hyperpolarization andexcitability which leads to flaccid paralysis that results inexpulsion of worm by peristaltic movement [33]

A series of twelve new N-substituted-2-hydroxyaceto-phenonimine derivatives 15(andashl) (Figure 15) was synthesizedby conventional as well as microwave method Synthesizedcompoundswere evaluated for their antinemic activity by cal-culating LC

50values of different synthesized imines against

J2s ofM incognita Carbofuran was employed as a standard

Although all the compounds possessed activity againstM incognita N-hexyl-2-hydroxyacetophenonimine (15j) N-hexyl-2-hydroxypropiophenonimine (15k) and N-propyl-2-hydroxypropiophenonimine (15l) were found to possesssignificant activity with LC

50values of 9960 7446 10953

and mgLminus1 respectively as compared to other imines Theabove observations enlightened that bioactivity increasedwith increase in chain length up to 6 carbon atoms whereasfurther increase in chain length decreased the activity [34]

24 Antitubercular Activity A novel series of forty-four17(indashxxxxiv) (Figure 17) Schiff bases of isonicotinic acidhydrazide (INH) was synthesized by structural modificationof 16 (Figure 16) in which hydrazine unit was chemicallyblocked at N2 position by deactivating acetylation by N-arylaminoacetyl transferase (NATs) enzyme The deacti-vation phenomenon seems to be associated with rise ofresistance Synthesized Schiff bases were blocked towardthe enzymatic deactivation process The results revealedthat compound 17(xv) was found to be the most potentantitubercular agentwithMIC005 120583gmL and logP 404 [35]

A series of Schiff bases of indoline-23-dione derivativesand nalidixic acid carbohydrazides 18(andashn) (Figure 18) wassynthesized and screened for antitubercular activity againstfour Mycobacterium strains (M xenopi M cheleneo Mintraccllulave and M smegmatis) using isonicotinic acidhydrazide as a standard drug Agar dilution method wasopted for screening the activity From the results compound18f was found to be themost potent antitubercular agent withMIC 0625 120583gmL which is 20 times higher than the MIC ofstandard drug (125120583gmL) [36]

Synthesis of six D-mannitol-derived Schiff bases19(andashf) (Figure 19) 16-dideoxy-16-bis-[(E)-arylmethylid-ene]amino-D-mannitol was carried out and synthesizedcompounds were evaluated for their in vitro antitubercularactivity against M tuberculosis H

37Rv by employing

microplate Alamar Blue assay (MABA) Compounds 19e19d and 19f have shown significant inhibitory activity whencompared with standard drug ethambutol (first-line drug)due to presence of nitro group while chlorine-containingcompounds (19a 19b and 19c) have shown resistance MICvalues for 19e 19d and 19f were found to be 125 250 and25 120583gmL respectively [37]


NH HN

NH HN

HO

HO

OH

OH

O

O O

O

M

11

M = Cu(II) Co(II) and Ni(II)

Figure 11

N

HO

OR H

H

EthylIsopropyl

t-Butyl4-Methyl phenyl

Benzyl2-Morpholine ethyl

2-Morpholine propylIsoheptyl

abcdefgh

R

12

12

Figure 12

O

O

O

H

NH H

O OH -CHOt-Butyl

IsopropylMethylHeptylEthyl

PropylButyl

2-Morpholilno ethyl

abcdefghi

R

13

13

Figure 13

N

N

O

N CH

R

a

b

c

N

Cl Cl

O

OH

HO d

e

R R

14

1414CH3

NO2

Figure 14


OH

R

R171715151410

866552

Rabcdef

ghijkl

15

15 15CH3

CH3

CH3

CH3

C2H5

C2H5

C2H5

C2H5

C2H5

C2H5

CH3

C2H5

n n

N(CH2)nCH3

Figure 15

N16

CON1HN2H2

Figure 16

N

xv H

17

17

CONHN=CR1R2

R1 R2

4-(CH=NNHCOC5H4N)C6H4

Figure 17

N

N

O

R

NH

O

N N

OR

a H Hb Hc Hd He Hf Hg H OH

h BrBrBrBrBrBrBr

ijklmn

R

18

18 18R1 R1

R1

CH2CH3

C3H7

-CH2CH=CH2

-CH2C6H5CH3

CH3

C2H5

H

OH

C3H7

-CH2CH=CH2

-CH2C6H5

CH3

C2H5

Figure 18

Cl H H H HH Cl H H HH H Cl H H

H H H HH H H HH H H H

abcdef

NN

OH

OHOH

OH

19

19R1

R1

R1

R2

R2 R2

R3

R3

R3

R4

R4

R4

R5

R5

R5

NO2

NO2

NO2

Figure 19


N

O

NH

N

Ar

abcdef

Rghijk

R

20

20 202-OHC6H5

4-OHC6H5

4-ClC6H4

4-NO2C6H5

2-NO2C6H4

4-FC6H4

4-OCH3C6H4

2-C4H3O4-(CH3)2NC6H4

4-(CH3)2NC6H4

4-OH 3-OHCH3C6H3

Figure 20

N OO

CONHN C

a H 4-OH g 4-Clb H hc H id 2-OH je 4-OH kf l

21

21 21

R1

R1 R2 R1 R2

R2

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

3-NO2

4-CH3

4-NO2

4-OCH3

2-NO2

24-(Cl)2

34(OCH3)2

2-OH OCH3

Figure 21

25 Antidepressant Activity Schiff bases of isonicotinoylhydrazoneN1015840-[(1Z)-(substituted aromatic)methylidene]pyr-idine-4-carbohydrazides 20(andashk) (Figure 20) were synthe-sized by green route of microwave synthesis and sonica-tion Synthesized compounds were evaluated for in vivoantidepressant and nootropic activities The results revealedthat the test compounds substituted with nitro halo-gen and dimethoxy groups exhibited significant antide-pressant and nootropic activities N1015840-[(1Z)-(25 dimethoxy-phenyl)methylidene]pyridine-4-carbohydrazide was foundto exhibit the highest antidepressant activity [38]

26 Anticonvulsant Activity A series of Schiff basesof phthalimide 4-(13-dioxo-13-dihydro-2H-isoindol-2-yl)-N1015840-(substituted phenyl)methyleneethylidene benzohydraz-ide 21(andashi) (Figure 21) was synthesized and evaluated foranticonvulsant and neurotoxic activities [39]

From the results it was concluded that all the compoundswere found to be active and less toxic than phenytoin whichwas employed as a standard drug Compound 21l substitutedwith nitro group at ortho position of distal aryl ring wasreported as the most potent anticonvulsant agent [39]

Synthesis of a series of 331015840[6-(23-dichlorophenyl)-124-triazine-35-diyl]dinitrolobis-(substituted-13-dihydro-2H-indol-2-one) 22 (Figure 22) of lamotrigine with isatin andsubstituted isatin was carried out and screened for theanticonvulsant activity MES (maximal electroshock seizure)

testmethodwas opted to carry out the anticonvulsant activityby incorporation of lamotrigine and phenobarbitone sodiumas standard drugs Results revealed that the synthesizedcompounds possessed better anticonvulsant activity than thestandard lamotrigine [40]

Some novel 3-aryl-4(3H)-quinazolinones-2-carboxalde-hydes and their corresponding Schiff bases 23 (Figure 23)and thiosemicarbazone derivatives have been synthesizedCompounds showed anticonvulsant analgesic and cytotoxicpotential due to thiosemicarbazone side chain at positionending with a free amino group and fluorine atom [41]

27 Anti-Inflammatory Analgesic and Nonulcerogenic Activi-ties A novel series of Schiff bases containing sydnone thatis 3-[1-(4-isobutylphenyl)ethyl]-4-(3-substituted-4-syd-nonylidene) amino 5-mercapto-124-triazoles 24(andashc)(Figure 24) was synthesized and screened for their anti-inflammatory and analgesic activities Results revealedthat compound 24c 3-[1-(4-isobutylphenyl)ethyl]-4-[3-(p-anisyl)-4-sydnonylidene] amino 5-mercapto-124-triazoleexhibited good anti-inflammatory and analgesic activities ascompared to 24a and 24b which indicated that presence ofelectron-releasing group in sydnone has resulted in betteranti-inflammatory and analgesic activities [42]

Synthesis of novel Schiff base analogues of 4-amino-15-dimethyl-2-phenylpyrazol-3-one 25(andashm) (Figure 25) wascarried out Synthesized compounds were screened for


NH

N

N N

N N

HN

Cl

Cl

O

O

-H-Cl

12

22

22

R1

R1

R1

Figure 22

N

NI

O

CH

NHN C

S

F

23

NH2

Figure 23

N

HN

N

N

ON

S

R

a Hbc

R

24

24

N+

minusO

CH3

CH3

CH3

H3COCH3

Figure 24

NN

N

O

f H OH OH H H

25

25 R1 R2 R3 R4 R5

R1

R2

R3

R4

R4

CH3H3C

Figure 25


Cl Cl

NH

26

CHONH=CHAr

Figure 26

N

N N

O

N

NN

SHF

O

N

R

Ra H gb hc 2-OH i 4-Cld

j 4-Fekf

R

27

27 27

4-CH3O

2-CH3O34-OCH2O

345-(CH3O)3 4-NO2

3-OH 4-CH3O4-OH 3-CH3O

Figure 27

the anti-inflammatory and antioxidant activities Compound25f was found to be the most potent anti-inflammatoryagent and antioxidant The anti-inflammatory activity of 25fwas evaluated in terms of its potential of nitric oxide (NO)production inhibition in LPS-pretreated RAW 2647 cellsusing the Griess method

Lipopolysaccharide (LPS) an endotoxin which is derivedfrom the cell wall of Gram-negative bacteria can inducemultiple signaling pathways to stimulate the production ofinflammatory modulators involving NO PGE

2 TNF-120572 and

interleukins The results indicated that 50120583gmL of 25finhibited the LPS-stimulated COX-2 mRNA levels [43]

A series of S-substituted phenacyl 134-oxadiazoles andSchiff bases 26(andashk) (Figure 26) derived from 2-[(26-dichlo-roanilino) phenyl] acetic acid (diclofenac acid) was syn-thesized and screened for the analgesic anti-inflammatoryand nonulcerogenic activities Acetic-acid-induced writhingtest and carrageenan-induced rat paw edema method wereemployed for analgesic and anti-inflammatory activitiesrespectively From the studies it was concluded that syn-thesized compounds were devoid of gastrointestinal toxic-ities Among all the synthesized compounds N-(4-bromo-benzylidene)-[2-(26-dichloroaniline)benzyl carbazide] 26kwas found to be themost potent anti-inflammatory agentTheanalgesic effect of 26k (6866) was found to be better thanthat of diclofenac sodium (6465) [44]

28 Antitumor Activity A novel series of fluoroquinoloneC-3 heterocycles (IV) that is s-triazole Schiff 27(andashk)(Figure 27) and mannich bases derivatives of ofloxacin was

synthesized and evaluated for in vitro antitumor activityagainst amurine leukemia cell line (L1210) a human leukocy-toma cell line (HL60) and a Chinese hamster ovary cell line(CHO) using theMTT assay From the observed results it wasconcluded that a free phenol group containing compounds27c 27g and 27h exhibited more potent activity than theother test compounds [45]

A series of thirteen quinolin-2(1H)-one-derived Schiffbases 28(andashm) (Figure 28) and their Cu(II) 29(andashm)(Figure 28) complexes was synthesized Selected compoundswere screened for their in vitro anticancer and antifungalactivities Human hepatic carcinoma cell line Hep-G

2was

employed for screening of the anticancer potential Cisplatinwas used as a standard drug for the comparison Screenedcompounds were found to be active antifungal agents andcompound (7E)-7-(3-ethoxy-2-hydroxybenzylideneamino)-4-methylquinolin-2(1H)-one was reported as a potentcytotoxic agent which enlightened the good potential ofCu(II) complexes of Schiff base ligands as therapeutic agents[46]

A series of three Schiff bases 4-([3-(4-substitutedphenyl)-1H-pyrazol-4-yl] methyleneamino)-5-[(substitutedphenoxy)methyl]-124-triazole-3-thiol 30(andashc) (Figure 29)was evaluated for their in vivo antitumor activity againstEhrlich-ascites-carcinoma-(EAC-) bearing Swiss albinomice Schiff bases were used in two different doses that is50mgkg and 100mgkg of the body weight of mice Meansurvival time (MST) and percentage increase in lifespan (ILS) that is total number of days an animal survived fromthe day of tumor inoculation were calculated Body weights


CH

N NH

O

d OH H H

CHN

O CuO N

HN O

NH

CHO

2829

2829

OC2H5

R1

R1

R2

R2

R2

R3

R3

R3

R3

R3

R4

R4

R4

R4

CH3

Figure 28

N

N

NO

RSH

N

NH

N

Ra 4-Methylbenzene Clb 4-Methylbenzene Fc 2-Methylbenzene F

30

30 R1

R1

Figure 29

of all animals were measured on days 0 3 5 7 10 12 and 14[47]

The results revealed that cisplatin (35mgkg ipsingle dose) significantly enhanced MST of EAC-infectedmice Among the three Schiff bases 4-([3-(4-fluoro-phenyl)-1H-pyrazol-4-yl]methyleneamino)-5-[(2 methyl-phenoxy)methyl]-124-triazole-3-thiol 30c at the dose of100mgkg body weight was found to enhance the meansurvival time of tumor-bearing mice MST and deviatedhematological parameters of infected mice were found to benormal after treatment with 30c [47]

29 Antioxidant Activity A series of substituted-N1015840-[(1E)-substituted phenylmethylidene]benzohydrazide analogs31(andashn) (Figure 30) was synthesized and evaluated for theirin vitro antioxidant anti-inflammatory and antimicrobialactivities The antioxidant activity of all the synthesizedcompounds was evaluated by the phosphomolybdenummethod Compounds 31c 31d and 31f were reported toshow good antioxidant activity due to presence of 4-nitro 4-methyl and 3-nitro groups respectively whereas 31a having4-hydroxy group did not possess such activity From theresults it can be concluded that substitutions like nitro andalkyl lead to enhancement in antioxidant activity throughone-electron transfer mechanism [48]

A new Schiff base ligand N-(2-hydroxylacetophenone)-3-oxapentane-15-diamine (HL) 32 and its Ni complex

[Ni2(L)2(NO3)2] 33 were synthesized and evaluated for

antioxidation and DNA-binding properties The complexshowed inhibitory activity and the suppression ratio of OHradical increases with increase in the concentration of thecomplex Mannitol and vitamin C were employed as thestandard antioxidants for comparison According to theresults the 50 inhibitory concentration (IC

50) value of 33

was found to be 81 plusmn 0078120583M whereas IC50

for mannitolwas 96 120583M and 32 was devoid of antioxidant activity Both32 and 33 bind to DNA in intercalationmode but the bindingstrength of 33 was found to be better than 32 [49]

210 Antiviral Activity A series of 3-(benzylideneamino)-2-phenylquinazoline-4(3H)-one 34(andashl) (Figure 31) was syn-thesized and evaluated for their cytotoxicity and antiviralactivity Compounds having 2-hydroxy substitution showedbetter antiviral activity [50]

A series of thiazolines and azetidinones was synthesizedby reaction of Schiff bases 35(andashi) (Figure 32) (intermediatereaction) with thioglycolic acid and chloral acetyl chloriderespectively Schiff bases were evaluated for antibacterial andantiviral (against HIV-I) potential All the compounds werefound to be good HIV-I inhibitors except 35f and 35g [51]

211 Antihypertensive Activity Schiff bases of 2-phenyl-3-(amino substituted arylidene)quinazoline-4-(3H)-ones36(a-b) (Figure 33) were synthesized and evaluated for


4-Cl4-Cl4-Cl4-Cl4-Cl4-Cl

abcdef

ghijklmn

Ar ArO

HN

N Ar

31

31 312-OHC6H4

4-NO2C6H4

4-NO2C6H4

4-CH3C6H4

4-CH3C6H4

2-OHC10H6

3-NO2C6H4

-C6H4

4-ClC6H4

R998400

R998400 R998400

2-OHC6H4

4-OHC6H4

2-NO2C6H4

2-COC6H5

2-COC6H5

2-COC6H5

2-COC6H5

2-COC6H5

2-COC6H5

2-COC6H5

2-COC6H5

3-OCH3 4-OHC6H3

3-OCH3 4-OHC6H3

Figure 30

N

NN

RO

RH 2-OHHHH

4-ClH H

H 4-OHH

4-OHH 4-ClHH

ghijkl

abcdef

R R

2-NO2

4-OCH3

4-N(CH3)23-OH 4-OCH3

2-OCH3

R998400 R998400

34

34 34

CH3

CH3

CH3

Figure 31

O

Cl Cl N=HC

R H2-OH4-OH

4-Cl

abcdefghi

R

4-NO2

4-OCH3

345-(OCH3)3

4-OH 3-OCH3

-CH=CH-C6H535

35

Figure 32

antihyperlipidemic activity Hyperlipidemia was induced inrats by atherogenic diet After 45 days levels of serum totalcholesterol (TC) and LDL cholesterol were recorded to be2316 plusmn 1435mgdL and 16453 plusmn 126mgdL which werecomparatively higher than normal rat serum TC (7136 plusmn1195mgdL) and LDL-C (10066 plusmn 088mgdL) levelswhereas serum HDL-C level was found to be lower (19012 plusmn066mgdL) as compared to the normal level (5066 plusmn088mgdL)

Results revealed that 36a reduced TC and LDL-C levelsto 17241 plusmn 41mgdL and 9110 plusmn 097mgdL and raisedserum HDL-C level to 6007 plusmn 067mgdL whereas 36breduced serum TC and LDL-C levels to 9363 plusmn 1292 and8135 plusmn 081mgdL and raised serum HDL-C level to 5940 plusmn045mgdL at the dose of 200mgkg po once daily [52]

212 Antidiabetic and Antiglycation Activities A series ofoxovanadium complexes with mixed ligands a bidentateNN ligand 37 and a tetradentate ONO-donor Schiff baseligand 38 (Figure 34) was synthesized and evaluated forprotein tyrosine phosphate (PTP) inhibition PTP1B has beenidentified as key enzyme related to insulin resistance Thusthe inhibition of PTP1B has emerged out as an importantapproach to enhance insulin sensitivity The kinetic analy-sis results revealed that oxovanadium complexes displayedpotent reversible competitive inhibition PTP1B with IC

50

values in low nanomolar range [53]A series of twenty-seven bis-Schiff base of isatin 39(indash

xxvii) (Figure 35) was synthesized and evaluated for their invitro antiglycation activity Compounds 39(xx) and 39(xxi)substituted with nitro groups at para and ortho positions


N

N

O

NR

Ra 2-OHb

36

36

4-OH 3-OMe

Figure 33

N

HC O

C

O

O

V NN

NN

Bipyridine phenanthroline dipyridoquinoxalinedipyridophenazine and methyldipyridophenazine

38

=

Figure 34

NH

O

N NH H HH H HH H H

xxxxivii

R1 R1

R2

R2

R3

R3

4-NO2C6H4

2-NO2C6H4

34-(OH)2C6H3

39

39 R4

R4

Figure 35

respectively were found to be the most potent antiglycationagents with IC

50(25761 plusmn 563 120583M) and 24395 plusmn 459 120583M

better than IC50

(29446 plusmn 150 120583M) of rutin which wasemployed as standard The 34-dihydroxy analog 39(vii) wasfound as the third most potent antiglycation agent with IC

50

(29114 plusmn 253120583M) [54]

3 Conclusion

Schiff bases are one of the most important chemical classesof compounds having a common integral feature of a varietyof medicinal agents This review reflects the contribution ofSchiff bases to the design and development of novel leadhaving potential biological activities with fewer side effectsThis bioactive core has maintained the interest of researchersin gaining the most suggestive and conclusive access in the

field of various Schiff bases of medicinal importance fromlast decades The present paper is an attempt to review all thebiological activities reported for Schiff bases in the currentliterature with an update of recent research findings

References

[1] Z Cimerman S Miljanic and N Galic ldquoSchiff bases derivedfrom aminopyridines as spectrofluorimetric analytical rea-gentsrdquo Croatica Chemica Acta vol 73 no 1 pp 81ndash95 2000

[2] H Schiff ldquoMittheilungen aus dem Universitatslaboratorium inPisa eine neue reihe organischer Basenrdquo Justus Liebigs Annalender Chemie vol 131 no 1 pp 118ndash119 1864

[3] D N Dhar and C L Taploo ldquoSchiff bases and their applica-tionsrdquo Journal of Scientific and Industrial Research vol 41 no 8pp 501ndash506 1982


[4] B S Sathe E Jaychandran V A Jagtap and G M SreenivasaldquoSynthesis characterization and anti-inflammatory evaluationof new fluorobenzothiazole schiff rsquos basesrdquo International Journalof Pharmaceutical Research and Development vol 3 no 3 pp164ndash169 2011

[5] S M Sondhi N Singh A Kumar O Lozach and L MeijerldquoSynthesis anti-inflammatory analgesic and kinase (CDK-1CDK-5 and GSK-3) inhibition activity evaluation of benz-imidazolebenzoxazole derivatives and some Schiff rsquos basesrdquoBioorganic and Medicinal Chemistry vol 14 no 11 pp 3758ndash3765 2006

[6] A Pandey D Dewangan S Verma AMishra and R DDubeyldquoSynthesis of schiff bases of 2-amino-5-aryl-134-thiadiazoleand its analgesic anti-inflammatory anti-bacterial and anti-tubercular activityrdquo International Journal of ChemTech Researchvol 3 no 1 pp 178ndash184 2011

[7] C Chandramouli M R Shivanand T B Nayanbhai BBheemachari and R H Udupi ldquoSynthesis and biologicalscreening of certain new triazole schiff bases and their deriva-tives bearing substituted benzothiazole moietyrdquo Journal ofChemical and Pharmaceutical Research vol 4 no 2 pp 1151ndash1159 2012

[8] R P Chinnasamy R Sundararajan and S Govindaraj ldquoSyn-thesis characterization and analgesic activity of novel schiffbase of isatin derivativesrdquo Journal of Advanced PharmaceuticalTechnology and Research vol 1 no 3 pp 342ndash347 2010

[9] K Mounika B Anupama J Pragathi and C GyanakumarildquoSynthesis characterization and biological activity of a Schiffbase derived from 3-ethoxy salicylaldehyde and 2-amino ben-zoic acid and its transition metal complexesrdquo Journal of Scien-tific Research vol 2 no 3 pp 513ndash524 2010

[10] P Venkatesh ldquoSynthesis characterization and antimicrobialactivity of various schiff bases complexes of Zn(II) and Cu(II)ionsrdquo Asian Journal of Pharmaceutical and Health Sciences vol1 no 1 pp 8ndash11 2011

[11] A K Chaubey and S N Pandeya ldquoSynthesis amp anticonvulsantactivity (Chemo Shock) of Schiff and Mannich bases of Isatinderivatives with 2-Amino pyridine (mechanism of action)rdquoInternational Journal of PharmTech Research vol 4 no 4 pp590ndash598 2012

[12] T Aboul-Fadl F A Mohammed and E A Hassan ldquoSynthesisantitubercular activity and pharmacokinetic studies of someSchiff bases derived from 1- alkylisatin and isonicotinic acidhydrazide (INH)rdquo Archives of Pharmacal Research vol 26 no10 pp 778ndash784 2003

[13] R Miri N Razzaghi-asl and M K Mohammadi ldquoQM studyand conformational analysis of an isatin Schiff base as apotential cytotoxic agentrdquo Journal of Molecular Modeling vol19 no 2 pp 727ndash735 2013

[14] S M M Ali M Abul Kalam Azad M Jesmin et al ldquoIn vivoanticancer activity of Vanillin semicarbazonerdquo Asian PacificJournal of Tropical Biomedicine vol 2 no 6 pp 438ndash442 2012

[15] D Wei N Li G Lu and K Yao ldquoSynthesis catalytic andbiological activity of novel dinuclear copper complexwith Schiffbaserdquo Science in China B vol 49 no 3 pp 225ndash229 2006

[16] P G Avaji C H Vinod Kumar S A Patil K N Shivanandaand C Nagaraju ldquoSynthesis spectral characterization in-vitromicrobiological evaluation and cytotoxic activities of novelmacrocyclic bis hydrazonerdquo European Journal of MedicinalChemistry vol 44 no 9 pp 3552ndash3559 2009

[17] K N Venugopala and B S Jayashree ldquoSynthesis of car-boxamides of 21015840-amino-41015840-(6-bromo-3-coumarinyl) thiazole

as analgesic and antiinflammatory agentsrdquo Indian Journal ofHeterocyclic Chemistry vol 12 no 4 pp 307ndash310 2003

[18] K Vashi and H B Naik ldquoSynthesis of novel Schiff baseand azetidinone derivatives and their antibacterial activityrdquoEuropean Journal of Chemistry vol 1 pp 272ndash276 2004

[19] S Li S Chen S Lei H Ma R Yu and D Liu ldquoInvestigationon some Schiff bases as HCl corrosion inhibitors for copperrdquoCorrosion Science vol 41 no 7 pp 1273ndash1287 1999

[20] Z H Chohan M Praveen and A Ghaffar ldquoStructural and bio-logical behaviour of Co(II) Cu(II) and Ni(II) metal complexesof some amino acid derived Schiff-basesrdquo Metal-Based Drugsvol 4 no 5 pp 267ndash272 1997

[21] S Ershad L Sagathforoush G Karim-Nezhad and S KangarildquoElectrochemical behavior of N

2SO Schiff-base Co(II) com-

plexes in non-aqueous media at the surface of solid electrodesrdquoInternational Journal of Electrochemical Science vol 4 no 6 pp846ndash854 2009

[22] F Tisato F Refosco and G Bandoli ldquoStructural survey oftechnetium complexesrdquo Coordination Chemistry Reviews vol135-136 pp 325ndash397 1994

[23] A Jarrahpour D Khalili E De Clercq C Salmi and JM Brunel ldquoSynthesis antibacterial antifungal and antiviralactivity evaluation of some new bis-Schiff bases of isatin andtheir derivativesrdquoMolecules vol 12 no 8 pp 1720ndash1730 2007

[24] A Bhattacharya VC Purohit and F Rinaldi ldquoEnvironmentallyfriendly solvent-free processes novel dual catalyst system inHenry reactionrdquo Organic Process Research and Developmentvol 7 no 3 pp 254ndash258 2003

[25] C R Prakash and S Raja ldquoSynthesis characterization andin vitro antimicrobial activity of some novel 5-substitutedSchiff and Mannich base of isatin derivativesrdquo Journal of SaudiChemical Society 2011

[26] N B Patel and J C Patel ldquoSynthesis and antimicrobial activityof Schiff bases and 2-azetidinones derived from quinazolin-4(3H)-onerdquoArabian Journal of Chemistry vol 4 no 4 pp 403ndash411 2011

[27] S Malladi A M Isloor S Isloor and D S Akhila ldquoSynthesischaracterization and antibacterial activity of some new pyrazolebased Schiff basesrdquo Arabian Journal of Chemistry vol 6 no 3pp 335ndash340 2013

[28] HH Essa F Kandil andA Falah ldquoSynthesis and identificationof schiff bases and biological activity new studyrdquo Iraqi Journal ofScience vol 53 no 2 pp 230ndash240 2012

[29] V A Shelke S M Jadhav V R Patharkar S G ShankarwarA S Munde and T K Chondhekar ldquoSynthesis spectroscopiccharacterization and thermal studies of some rare earth metalcomplexes of unsymmetrical tetradentate Schiff base ligandrdquoArabian Journal of Chemistry vol 5 pp 501ndash507 2012

[30] R A Sheikh M Y Wani S Shreaz and A A HashmildquoSynthesis characterization and biological screening of someSchiff basemacrocyclic ligand based transitionmetal complexesas antifungal agentsrdquo Arabian Journal of Chemistry 2011

[31] K V Sashidhara A Kumar G Bhatia M M Khan A KKhanna and J K Saxena ldquoAntidyslipidemic and antioxidativeactivities of 8-hydroxyquinoline derived novel keto-enamineSchiffs basesrdquo European Journal of Medicinal Chemistry vol 44no 4 pp 1813ndash1818 2009

[32] K V Sashidhara J N Rosaiah G Bhatia and J K SaxenaldquoNovel keto-enamine Schiffs bases from7-hydroxy-4-methyl-2-oxo-2H-benzo[h] chromene-810-dicarbaldehyde as potentialantidyslipidemic and antioxidant agentsrdquo European Journal ofMedicinal Chemistry vol 43 no 11 pp 2592ndash2596 2008


[33] H D Revanasiddappa K S Prasad L S Kumar and BJayalakshmi ldquoSynthesis and biological activity of new schiffbases containing 4(3H)-quinazolinone ring systemrdquo Interna-tional Journal of ChemTech Research vol 2 no 2 pp 1344ndash13492010

[34] A Kundu N A Shakil D B Saxena P Pankaj J Kumarand S Walia ldquoMicrowave assisted solvent-free synthesis andbiological activities of novel imines (Schiff bases)rdquo Journal ofEnvironmental Science and Health B vol 44 no 5 pp 428ndash4342009

[35] M JHearnMHCynamonM F Chen et al ldquoPreparation andantitubercular activities in vitro and in vivo of novel Schiff basesof isoniazidrdquo European Journal of Medicinal Chemistry vol 44no 10 pp 4169ndash4178 2009

[36] T Aboul-Fadl F A S Bin-Jubair and O Aboul-Wafa ldquoSchiffbases of indoline-23-dione (isatin) derivatives and nalidixicacid carbohydrazide synthesis antitubercular activity andpharmacophoric model buildingrdquo European Journal of Medic-inal Chemistry vol 45 no 10 pp 4578ndash4586 2010

[37] M D L Ferreira T R A Vasconcelos E M de Carvalhoet al ldquoSynthesis and antitubercular activity of novel Schiff basesderived from d-mannitolrdquo Carbohydrate Research vol 344 no15 pp 2042ndash2047 2009

[38] A B Thomas R K Nanda L P Kothapalli and S C HamaneldquoSynthesis and biological evaluation of Schiff rsquos bases and 2-azetidinones of isonicotinyl hydrazone as potential antidepres-sant and nootropic agentsrdquo Arabian Journal of Chemistry 2011

[39] M A Bhat and M A Al-Omar ldquoSynthesis characterizationand in vivo anticonvulsant and neurotoxicity screening of Schiffbases of phthalimiderdquoActa Poloniae Pharmaceutica vol 68 no3 pp 375ndash380 2011

[40] A A Kulkarni S B Wankhede N D Dhawale P B YadavV V Deore and I D Gonjari ldquoSynthesis characterization andbiological behavior of some Schiff rsquos and Mannich base deriva-tives of anticonvulsant drugsrdquo Arabian Journal of Chemistryhttpdxdoiorg101016jarabjc201207020

[41] M M Aly Y A Mohamed K A M El-Bayouki W MBasyouni and S Y Abbas ldquoSynthesis of some new 4(3H)-quin-azolinone-2-carboxaldehyde thiosemicarbazones and theirmetal complexes and a study on their anticonvulsant analgesiccytotoxic and antimicrobial activities e Part-1rdquo EuropeanJournal of Medicinal Chemistry vol 45 no 8 pp 3365ndash33732010

[42] Nithinchandra B Kalluraya S Aamir and A R ShabarayaldquoRegioselective reaction synthesis characterization and phar-macological activity of some new Mannich and Schiff basescontaining sydnonerdquo European Journal of Medicinal Chemistryvol 54 pp 597ndash604 2012

[43] M S Alam J Choi and D Lee ldquoSynthesis of novel Schiffbase analogues of 4-amino-1 5-dimethyl-2- phenylpyrazol-3-one and their evaluation for antioxidant and anti-inflammatoryactivityrdquo Bioorganic amp Medicinal Chemistry vol 20 pp 4103ndash4108 2012

[44] S V Bhandari K G Bothara M K Raut A A Patil AP Sarkate and V J Mokale ldquoDesign synthesis and evalua-tion of antiinflammatory analgesic and ulcerogenicity studiesof novel S-substituted phenacyl-134-oxadiazole-2-thiol andSchiff bases of diclofenac acid as nonulcerogenic derivativesrdquoBioorganic andMedicinal Chemistry vol 16 no 4 pp 1822ndash18312008

[45] G Hu G Wang N Duan et al ldquoDesign synthesis andantitumor activities of fluoroquinolone C-3 heterocycles(IV)

s-triazole Schiff-Mannich bases derived from ofloxacinrdquo ActaPharmaceutica Sinica B vol 2 no 3 pp 312ndash317 2012

[46] B S Creaven B Duff D A Egan et al ldquoAnticancer andantifungal activity of copper(II) complexes of quinolin-2(1H)-one-derived Schiff basesrdquo Inorganica Chimica Acta vol 363 no14 pp 4048ndash4058 2010

[47] S Dhanya A M Isloor P Shetty P G Nayak and K S R PaildquoIn vivo anticancer and histopathology studies of Schiff bases onEhrlich ascitic carcinoma cellsrdquo Arabian Journal of Chemistry2010

[48] S Bala GUppal S Kamboj V Saini andDN Prasad ldquoDesigncharacterization computational studies and pharmacologicalevaluation of substituted-N1015840-[(1E) substitutedphenylmethyli-dene]benzohydrazide analogsrdquo Medicinal Chemistry Researchvol 21 no 11 pp 1ndash13 2012

[49] H Wu F Jia F Kou B Liu J Yuan and Y Bai ldquoA Schiffbase ligand N-(2-hydroxylacetophenone)-3-oxapentane-1 5-diamine and its nickel(II)complex Synthesiscrystal struc-tureantioxidation and DNA-binding propertiesrdquo TransitionMetal Chemistry vol 36 no 8 pp 847ndash853 2011

[50] K S Kumar S Ganguly R Veerasamy and E De Clercq ldquoSyn-thesis antiviral activity and cytotoxicity evaluation of Schiffbases of some 2-phenyl quinazoline-4(3)H-onesrdquo EuropeanJournal of Medicinal Chemistry vol 45 no 11 pp 5474ndash54792010

[51] R N Patel P V Patel K R Desai P Y Purohit K S Nimavatand K B Vyas ldquoSynthesis of new heterocyclic schiff base thia-zolidinone and azetidinone compounds and their antibacterialactivity and anti-hiv activitiesrdquoHeterocyclic Letters vol 2 no 1pp 99ndash105 2012

[52] S GanguliM Firdous T SMaity R K Bera andM PanigrahildquoThe study of antihyperlipidemic activities of schiff bases of4(3H) quinazolinone derivatives in ratsrdquo International Journalof Pharmacy and Pharmaceutical Sciences vol 4 no 2 pp 175ndash178 2012

[53] C Yuan L Lu X Gao et al ldquoTernary oxovanadium(IV)complexes of ONO-donor Schiff base and polypyridyl deriva-tives as protein tyrosine phosphatase inhibitors synthesischaracterization and biological activitiesrdquo Journal of BiologicalInorganic Chemistry vol 14 no 6 pp 841ndash851 2009

[54] K M Khan M Khan M Ali et al ldquoSynthesis of bis-Schiffbases of isatins and their antiglycation activityrdquo Bioorganic andMedicinal Chemistry vol 17 no 22 pp 7795ndash7801 2009

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Inorganic ChemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

International Journal ofPhotoenergy


Carbohydrate Chemistry

International Journal of


Journal of

Chemistry


Advances in

Physical Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom

Analytical Methods in Chemistry

Journal of

Volume 2014

Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

SpectroscopyInternational Journal of


The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Medicinal ChemistryInternational Journal of


Chromatography Research International


Applied ChemistryJournal of



Theoretical ChemistryJournal of


Journal of

Spectroscopy

Analytical ChemistryInternational Journal of


Journal of


Quantum Chemistry


Organic Chemistry International

ElectrochemistryInternational Journal of



CatalystsJournal of


N

F

O

N

NN

N CH

Ar Ar Ar

F

N

COOHO

abcdef

ghijkl

1

1 1-C6H5

-4Cl-C6H4

-4OH-C6H4

-4OCH3-C6H4

-4NO2-C6H4

-6OH-C6H4

-4CH3-C6H4

-5NO2-C6H4

-4N(CH3)2-C6H4

-CH=HC-C6H4

-345(OCH3)3-C6H4

-4OH 5-OCH3-C6H4

Figure 1

CH

N NN

HN

Cl

Cl

OBr

R Ra gb hc

id

jekf

R2-NO2

3-NO2

2-OH4-OH2-Cl4-Cl

2

2 24-OCH3

4-N(CH3)2

345-(OCH3)3

2-OH 4-OCH3

2-OH 4-N(C2H5)2

Figure 2

A novel series of Schiff bases that is 6-bromo-2-[2-(26-dichlorophenyl)amino]benzyl-3-(substituted benzyl-ideneamino)-quinazolin-4(3H)-one 2(andashk) (Figure 2) hasbeen synthesized and subjected to antimicrobial activity [26]

Evaluation was carried out for the in vitro antimicrobialactivity by cup platemethod For this S aureus P aeruginosaB subtilis and C albicans were employed Penicillin Gand amphotericin B were taken as standard drugs Resultsrevealed that all compounds have moderate to poor antifun-gal activity and good antibacterial activity [26]

A novel series of pyrazole-based Schiff bases 3(andashj)(Figure 3) 4-[(3-substituted-1H-pyrazol-3-yl)methyleneam-ino]-5-substituted-4H-124-triazole-3-thiols was synthe-sized and screened for antibacterial activity against themicrobial strains of S aureus P aeruginosa B subtilis and Ecoli From the results compound 3f was found to be equallyas active as standard drug ceftriaxone against P aeruginosaB subtilis and E coli and most active against S aureus [27]

Synthesis of new open (4ndash6) (Figures 4ndash6) and macro-cyclic (7) (Figure 7) Schiff bases has been done and evaluatedfor the antimicrobial activity Open Schiff bases were synthe-sized by the condensation of salicylaldehyde and o-vanillinwith 441015840-diaminodiphenylmethane 441015840-diamino diphenylsulphide and diethyl ester of terephthalic acid respectively

Macrocyclic Schiff bases were reported as the con-densation product of 16-bis(2-formylphenyl)hexane with

thiocarbohydrazide In order to test the biological activityof the synthesized compounds four microorganisms (Kpneumoniae E coli S aureus and S typhimurium) wereemployed All the synthesized compounds were found to bemoderate to strongly active [28]

A few novel solid complexes 8 (Figure 8) of La(III)Ce(III) Pr(III) Nd(III) Sm(III) and Gd(III) with Schiffbase that is 9 (Figure 9) 4-hydroxy-3-(1-2-(2-hydroxy-benzylidene)-amino-phenylimino-ethyl)-6-methyl-pyran-2-ones were synthesized and screened for the antibacterialactivity against S aureus E coli and Bacillus species andantifungal activity against A niger Trichoderma andF oxysporum Results revealed that the complexes werebiologically active and have exhibited enhanced antimicro-bial activity than the free ligand (Schiff base) [29]

Some novel Schiff bases macrocyclic tetradentate nitro-gen donor (N

4) 671415-tetrahydroxy-14912-tetraazacyclo-

hexadecane-581316-tetrone ligand-based metal complexes11 (Figure 11) from 10 (Figure 10) were synthesized andscreened for the in vitro antifungal activity and toxicitystudies Minimum inhibitory concentration (MIC) alongwith ergosterol composition assay against C albicans (ATCC10261) C glabrata (ATCC 90030) and C tropicalis (ATCC750) was performed The antimicrobial results indicated thatall the synthesized compoundswere found to be active againstall fungal strains It was observed that Ni(II) complex and


N

N

N

R SH

N

NH

N

R Ra f HH

b g H

c h H

d i H

e j3

3 3

R1

R1 R1

-C2H5

-C2H5

-C2H5

-C2H5

-C2H5

4-OCH3

4-F

4-Cl

H

4-OCH3

4-F

4-F

4-Cl

-C3H724-Cl2

Figure 3

OH

CHN

C

N

HC

HO

H2

4

Figure 4

OH

CH

N

S

N

HC

HO5

Figure 5

OH

HCN

HN C

O

C

O

NH

NCH

HO

OCH3 H3CO

6

Figure 6

CHN

HN

S

N NCH HC

O O

7

Figure 7

O OM

O

N NO

8

H2O

CH3

OH2

NO3

H3C

H3C


Figure 8




O OH

O N NH

HO

9

H3C

H3C

Figure 9

NH HN

NH HN

HO

HO

OH

OH

O

O O

O

10

Figure 10










50values of 9960 7446 10953





37Rv by employing



NH HN

NH HN

HO

HO

OH

OH

O

O O

O

M

11


Figure 11

N

HO

OR H

H

EthylIsopropyl




abcdefgh

R

12

12

Figure 12

O

O

O

H

NH H

O OH -CHOt-Butyl


PropylButyl

2-Morpholilno ethyl

abcdefghi

R

13

13

Figure 13

N

N

O

N CH

R

a

b

c

N

Cl Cl

O

OH

HO d

e

R R

14

1414CH3

NO2

Figure 14


OH

R

R171715151410

866552

Rabcdef

ghijkl

15

15 15CH3

CH3

CH3

CH3

C2H5

C2H5

C2H5

C2H5

C2H5

C2H5

CH3

C2H5

n n

N(CH2)nCH3

Figure 15

N16

CON1HN2H2

Figure 16

N

xv H

17

17

CONHN=CR1R2

R1 R2


Figure 17

N

N

O

R

NH

O

N N

OR


h BrBrBrBrBrBrBr

ijklmn

R

18

18 18R1 R1

R1

CH2CH3

C3H7

-CH2CH=CH2

-CH2C6H5CH3

CH3

C2H5

H

OH

C3H7

-CH2CH=CH2

-CH2C6H5

CH3

C2H5

Figure 18



abcdef

NN

OH

OHOH

OH

19

19R1

R1

R1

R2

R2 R2

R3

R3

R3

R4

R4

R4

R5

R5

R5

NO2

NO2

NO2

Figure 19


N

O

NH

N

Ar

abcdef

Rghijk

R

20

20 202-OHC6H5

4-OHC6H5

4-ClC6H4

4-NO2C6H5

2-NO2C6H4

4-FC6H4

4-OCH3C6H4


4-(CH3)2NC6H4

4-OH 3-OHCH3C6H3

Figure 20

N OO

CONHN C


21

21 21

R1

R1 R2 R1 R2

R2

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

3-NO2

4-CH3

4-NO2

4-OCH3

2-NO2

24-(Cl)2

34(OCH3)2

2-OH OCH3

Figure 21










NH

N

N N

N N

HN

Cl

Cl

O

O

-H-Cl

12

22

22

R1

R1

R1

Figure 22

N

NI

O

CH

NHN C

S

F

23

NH2

Figure 23

N

HN

N

N

ON

S

R

a Hbc

R

24

24

N+

minusO

CH3

CH3

CH3

H3COCH3

Figure 24

NN

N

O

f H OH OH H H

25

25 R1 R2 R3 R4 R5

R1

R2

R3

R4

R4

CH3H3C

Figure 25


Cl Cl

NH

26

CHONH=CHAr

Figure 26

N

N N

O

N

NN

SHF

O

N

R


j 4-Fekf

R

27

27 27

4-CH3O

2-CH3O34-OCH2O

345-(CH3O)3 4-NO2


Figure 27



2 TNF-120572 and






2was




CH

N NH

O

d OH H H

CHN

O CuO N

HN O

NH

CHO

2829

2829

OC2H5

R1

R1

R2

R2

R2

R3

R3

R3

R3

R3

R4

R4

R4

R4

CH3

Figure 28

N

N

NO

RSH

N

NH

N


30

30 R1

R1

Figure 29







50) value of 33








abcdef

ghijklmn

Ar ArO

HN

N Ar

31

31 312-OHC6H4

4-NO2C6H4

4-NO2C6H4

4-CH3C6H4

4-CH3C6H4

2-OHC10H6

3-NO2C6H4

-C6H4

4-ClC6H4

R998400

R998400 R998400

2-OHC6H4

4-OHC6H4

2-NO2C6H4

2-COC6H5

2-COC6H5

2-COC6H5

2-COC6H5

2-COC6H5

2-COC6H5

2-COC6H5

2-COC6H5

3-OCH3 4-OHC6H3

3-OCH3 4-OHC6H3

Figure 30

N

NN

RO

RH 2-OHHHH

4-ClH H

H 4-OHH

4-OHH 4-ClHH

ghijkl

abcdef

R R

2-NO2

4-OCH3


2-OCH3

R998400 R998400

34

34 34

CH3

CH3

CH3

Figure 31

O

Cl Cl N=HC

R H2-OH4-OH

4-Cl

abcdefghi

R

4-NO2

4-OCH3

345-(OCH3)3

4-OH 3-OCH3

-CH=CH-C6H535

35

Figure 32




50




N

N

O

NR

Ra 2-OHb

36

36

4-OH 3-OMe

Figure 33

N

HC O

C

O

O

V NN

NN


38

=

Figure 34

NH

O

N NH H HH H HH H H

xxxxivii

R1 R1

R2

R2

R3

R3

4-NO2C6H4

2-NO2C6H4

34-(OH)2C6H3

39

39 R4

R4

Figure 35



better than IC50


50

(29114 plusmn 253120583M) [54]

3 Conclusion



References






































































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of


N

N

N

R SH

N

NH

N

R Ra f HH

b g H

c h H

d i H

e j3

3 3

R1

R1 R1

-C2H5

-C2H5

-C2H5

-C2H5

-C2H5

4-OCH3

4-F

4-Cl

H

4-OCH3

4-F

4-F

4-Cl

-C3H724-Cl2

Figure 3

OH

CHN

C

N

HC

HO

H2

4

Figure 4

OH

CH

N

S

N

HC

HO5

Figure 5

OH

HCN

HN C

O

C

O

NH

NCH

HO

OCH3 H3CO

6

Figure 6

CHN

HN

S

N NCH HC

O O

7

Figure 7

O OM

O

N NO

8

H2O

CH3

OH2

NO3

H3C

H3C


Figure 8




O OH

O N NH

HO

9

H3C

H3C

Figure 9

NH HN

NH HN

HO

HO

OH

OH

O

O O

O

10

Figure 10










50values of 9960 7446 10953





37Rv by employing



NH HN

NH HN

HO

HO

OH

OH

O

O O

O

M

11


Figure 11

N

HO

OR H

H

EthylIsopropyl




abcdefgh

R

12

12

Figure 12

O

O

O

H

NH H

O OH -CHOt-Butyl


PropylButyl

2-Morpholilno ethyl

abcdefghi

R

13

13

Figure 13

N

N

O

N CH

R

a

b

c

N

Cl Cl

O

OH

HO d

e

R R

14

1414CH3

NO2

Figure 14


OH

R

R171715151410

866552

Rabcdef

ghijkl

15

15 15CH3

CH3

CH3

CH3

C2H5

C2H5

C2H5

C2H5

C2H5

C2H5

CH3

C2H5

n n

N(CH2)nCH3

Figure 15

N16

CON1HN2H2

Figure 16

N

xv H

17

17

CONHN=CR1R2

R1 R2


Figure 17

N

N

O

R

NH

O

N N

OR


h BrBrBrBrBrBrBr

ijklmn

R

18

18 18R1 R1

R1

CH2CH3

C3H7

-CH2CH=CH2

-CH2C6H5CH3

CH3

C2H5

H

OH

C3H7

-CH2CH=CH2

-CH2C6H5

CH3

C2H5

Figure 18



abcdef

NN

OH

OHOH

OH

19

19R1

R1

R1

R2

R2 R2

R3

R3

R3

R4

R4

R4

R5

R5

R5

NO2

NO2

NO2

Figure 19


N

O

NH

N

Ar

abcdef

Rghijk

R

20

20 202-OHC6H5

4-OHC6H5

4-ClC6H4

4-NO2C6H5

2-NO2C6H4

4-FC6H4

4-OCH3C6H4


4-(CH3)2NC6H4

4-OH 3-OHCH3C6H3

Figure 20

N OO

CONHN C


21

21 21

R1

R1 R2 R1 R2

R2

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

3-NO2

4-CH3

4-NO2

4-OCH3

2-NO2

24-(Cl)2

34(OCH3)2

2-OH OCH3

Figure 21










NH

N

N N

N N

HN

Cl

Cl

O

O

-H-Cl

12

22

22

R1

R1

R1

Figure 22

N

NI

O

CH

NHN C

S

F

23

NH2

Figure 23

N

HN

N

N

ON

S

R

a Hbc

R

24

24

N+

minusO

CH3

CH3

CH3

H3COCH3

Figure 24

NN

N

O

f H OH OH H H

25

25 R1 R2 R3 R4 R5

R1

R2

R3

R4

R4

CH3H3C

Figure 25


Cl Cl

NH

26

CHONH=CHAr

Figure 26

N

N N

O

N

NN

SHF

O

N

R


j 4-Fekf

R

27

27 27

4-CH3O

2-CH3O34-OCH2O

345-(CH3O)3 4-NO2


Figure 27



2 TNF-120572 and






2was




CH

N NH

O

d OH H H

CHN

O CuO N

HN O

NH

CHO

2829

2829

OC2H5

R1

R1

R2

R2

R2

R3

R3

R3

R3

R3

R4

R4

R4

R4

CH3

Figure 28

N

N

NO

RSH

N

NH

N


30

30 R1

R1

Figure 29







50) value of 33








abcdef

ghijklmn

Ar ArO

HN

N Ar

31

31 312-OHC6H4

4-NO2C6H4

4-NO2C6H4

4-CH3C6H4

4-CH3C6H4

2-OHC10H6

3-NO2C6H4

-C6H4

4-ClC6H4

R998400

R998400 R998400

2-OHC6H4

4-OHC6H4

2-NO2C6H4

2-COC6H5

2-COC6H5

2-COC6H5

2-COC6H5

2-COC6H5

2-COC6H5

2-COC6H5

2-COC6H5

3-OCH3 4-OHC6H3

3-OCH3 4-OHC6H3

Figure 30

N

NN

RO

RH 2-OHHHH

4-ClH H

H 4-OHH

4-OHH 4-ClHH

ghijkl

abcdef

R R

2-NO2

4-OCH3


2-OCH3

R998400 R998400

34

34 34

CH3

CH3

CH3

Figure 31

O

Cl Cl N=HC

R H2-OH4-OH

4-Cl

abcdefghi

R

4-NO2

4-OCH3

345-(OCH3)3

4-OH 3-OCH3

-CH=CH-C6H535

35

Figure 32




50




N

N

O

NR

Ra 2-OHb

36

36

4-OH 3-OMe

Figure 33

N

HC O

C

O

O

V NN

NN


38

=

Figure 34

NH

O

N NH H HH H HH H H

xxxxivii

R1 R1

R2

R2

R3

R3

4-NO2C6H4

2-NO2C6H4

34-(OH)2C6H3

39

39 R4

R4

Figure 35



better than IC50


50

(29114 plusmn 253120583M) [54]

3 Conclusion



References






































































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of


O OH

O N NH

HO

9

H3C

H3C

Figure 9

NH HN

NH HN

HO

HO

OH

OH

O

O O

O

10

Figure 10










50values of 9960 7446 10953





37Rv by employing



NH HN

NH HN

HO

HO

OH

OH

O

O O

O

M

11


Figure 11

N

HO

OR H

H

EthylIsopropyl




abcdefgh

R

12

12

Figure 12

O

O

O

H

NH H

O OH -CHOt-Butyl


PropylButyl

2-Morpholilno ethyl

abcdefghi

R

13

13

Figure 13

N

N

O

N CH

R

a

b

c

N

Cl Cl

O

OH

HO d

e

R R

14

1414CH3

NO2

Figure 14


OH

R

R171715151410

866552

Rabcdef

ghijkl

15

15 15CH3

CH3

CH3

CH3

C2H5

C2H5

C2H5

C2H5

C2H5

C2H5

CH3

C2H5

n n

N(CH2)nCH3

Figure 15

N16

CON1HN2H2

Figure 16

N

xv H

17

17

CONHN=CR1R2

R1 R2


Figure 17

N

N

O

R

NH

O

N N

OR


h BrBrBrBrBrBrBr

ijklmn

R

18

18 18R1 R1

R1

CH2CH3

C3H7

-CH2CH=CH2

-CH2C6H5CH3

CH3

C2H5

H

OH

C3H7

-CH2CH=CH2

-CH2C6H5

CH3

C2H5

Figure 18



abcdef

NN

OH

OHOH

OH

19

19R1

R1

R1

R2

R2 R2

R3

R3

R3

R4

R4

R4

R5

R5

R5

NO2

NO2

NO2

Figure 19


N

O

NH

N

Ar

abcdef

Rghijk

R

20

20 202-OHC6H5

4-OHC6H5

4-ClC6H4

4-NO2C6H5

2-NO2C6H4

4-FC6H4

4-OCH3C6H4


4-(CH3)2NC6H4

4-OH 3-OHCH3C6H3

Figure 20

N OO

CONHN C


21

21 21

R1

R1 R2 R1 R2

R2

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

3-NO2

4-CH3

4-NO2

4-OCH3

2-NO2

24-(Cl)2

34(OCH3)2

2-OH OCH3

Figure 21










NH

N

N N

N N

HN

Cl

Cl

O

O

-H-Cl

12

22

22

R1

R1

R1

Figure 22

N

NI

O

CH

NHN C

S

F

23

NH2

Figure 23

N

HN

N

N

ON

S

R

a Hbc

R

24

24

N+

minusO

CH3

CH3

CH3

H3COCH3

Figure 24

NN

N

O

f H OH OH H H

25

25 R1 R2 R3 R4 R5

R1

R2

R3

R4

R4

CH3H3C

Figure 25


Cl Cl

NH

26

CHONH=CHAr

Figure 26

N

N N

O

N

NN

SHF

O

N

R


j 4-Fekf

R

27

27 27

4-CH3O

2-CH3O34-OCH2O

345-(CH3O)3 4-NO2


Figure 27



2 TNF-120572 and






2was




CH

N NH

O

d OH H H

CHN

O CuO N

HN O

NH

CHO

2829

2829

OC2H5

R1

R1

R2

R2

R2

R3

R3

R3

R3

R3

R4

R4

R4

R4

CH3

Figure 28

N

N

NO

RSH

N

NH

N


30

30 R1

R1

Figure 29







50) value of 33








abcdef

ghijklmn

Ar ArO

HN

N Ar

31

31 312-OHC6H4

4-NO2C6H4

4-NO2C6H4

4-CH3C6H4

4-CH3C6H4

2-OHC10H6

3-NO2C6H4

-C6H4

4-ClC6H4

R998400

R998400 R998400

2-OHC6H4

4-OHC6H4

2-NO2C6H4

2-COC6H5

2-COC6H5

2-COC6H5

2-COC6H5

2-COC6H5

2-COC6H5

2-COC6H5

2-COC6H5

3-OCH3 4-OHC6H3

3-OCH3 4-OHC6H3

Figure 30

N

NN

RO

RH 2-OHHHH

4-ClH H

H 4-OHH

4-OHH 4-ClHH

ghijkl

abcdef

R R

2-NO2

4-OCH3


2-OCH3

R998400 R998400

34

34 34

CH3

CH3

CH3

Figure 31

O

Cl Cl N=HC

R H2-OH4-OH

4-Cl

abcdefghi

R

4-NO2

4-OCH3

345-(OCH3)3

4-OH 3-OCH3

-CH=CH-C6H535

35

Figure 32




50




N

N

O

NR

Ra 2-OHb

36

36

4-OH 3-OMe

Figure 33

N

HC O

C

O

O

V NN

NN


38

=

Figure 34

NH

O

N NH H HH H HH H H

xxxxivii

R1 R1

R2

R2

R3

R3

4-NO2C6H4

2-NO2C6H4

34-(OH)2C6H3

39

39 R4

R4

Figure 35



better than IC50


50

(29114 plusmn 253120583M) [54]

3 Conclusion



References






































































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of


NH HN

NH HN

HO

HO

OH

OH

O

O O

O

M

11


Figure 11

N

HO

OR H

H

EthylIsopropyl




abcdefgh

R

12

12

Figure 12

O

O

O

H

NH H

O OH -CHOt-Butyl


PropylButyl

2-Morpholilno ethyl

abcdefghi

R

13

13

Figure 13

N

N

O

N CH

R

a

b

c

N

Cl Cl

O

OH

HO d

e

R R

14

1414CH3

NO2

Figure 14


OH

R

R171715151410

866552

Rabcdef

ghijkl

15

15 15CH3

CH3

CH3

CH3

C2H5

C2H5

C2H5

C2H5

C2H5

C2H5

CH3

C2H5

n n

N(CH2)nCH3

Figure 15

N16

CON1HN2H2

Figure 16

N

xv H

17

17

CONHN=CR1R2

R1 R2


Figure 17

N

N

O

R

NH

O

N N

OR


h BrBrBrBrBrBrBr

ijklmn

R

18

18 18R1 R1

R1

CH2CH3

C3H7

-CH2CH=CH2

-CH2C6H5CH3

CH3

C2H5

H

OH

C3H7

-CH2CH=CH2

-CH2C6H5

CH3

C2H5

Figure 18



abcdef

NN

OH

OHOH

OH

19

19R1

R1

R1

R2

R2 R2

R3

R3

R3

R4

R4

R4

R5

R5

R5

NO2

NO2

NO2

Figure 19


N

O

NH

N

Ar

abcdef

Rghijk

R

20

20 202-OHC6H5

4-OHC6H5

4-ClC6H4

4-NO2C6H5

2-NO2C6H4

4-FC6H4

4-OCH3C6H4


4-(CH3)2NC6H4

4-OH 3-OHCH3C6H3

Figure 20

N OO

CONHN C


21

21 21

R1

R1 R2 R1 R2

R2

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

3-NO2

4-CH3

4-NO2

4-OCH3

2-NO2

24-(Cl)2

34(OCH3)2

2-OH OCH3

Figure 21










NH

N

N N

N N

HN

Cl

Cl

O

O

-H-Cl

12

22

22

R1

R1

R1

Figure 22

N

NI

O

CH

NHN C

S

F

23

NH2

Figure 23

N

HN

N

N

ON

S

R

a Hbc

R

24

24

N+

minusO

CH3

CH3

CH3

H3COCH3

Figure 24

NN

N

O

f H OH OH H H

25

25 R1 R2 R3 R4 R5

R1

R2

R3

R4

R4

CH3H3C

Figure 25


Cl Cl

NH

26

CHONH=CHAr

Figure 26

N

N N

O

N

NN

SHF

O

N

R


j 4-Fekf

R

27

27 27

4-CH3O

2-CH3O34-OCH2O

345-(CH3O)3 4-NO2


Figure 27



2 TNF-120572 and






2was




CH

N NH

O

d OH H H

CHN

O CuO N

HN O

NH

CHO

2829

2829

OC2H5

R1

R1

R2

R2

R2

R3

R3

R3

R3

R3

R4

R4

R4

R4

CH3

Figure 28

N

N

NO

RSH

N

NH

N


30

30 R1

R1

Figure 29







50) value of 33








abcdef

ghijklmn

Ar ArO

HN

N Ar

31

31 312-OHC6H4

4-NO2C6H4

4-NO2C6H4

4-CH3C6H4

4-CH3C6H4

2-OHC10H6

3-NO2C6H4

-C6H4

4-ClC6H4

R998400

R998400 R998400

2-OHC6H4

4-OHC6H4

2-NO2C6H4

2-COC6H5

2-COC6H5

2-COC6H5

2-COC6H5

2-COC6H5

2-COC6H5

2-COC6H5

2-COC6H5

3-OCH3 4-OHC6H3

3-OCH3 4-OHC6H3

Figure 30

N

NN

RO

RH 2-OHHHH

4-ClH H

H 4-OHH

4-OHH 4-ClHH

ghijkl

abcdef

R R

2-NO2

4-OCH3


2-OCH3

R998400 R998400

34

34 34

CH3

CH3

CH3

Figure 31

O

Cl Cl N=HC

R H2-OH4-OH

4-Cl

abcdefghi

R

4-NO2

4-OCH3

345-(OCH3)3

4-OH 3-OCH3

-CH=CH-C6H535

35

Figure 32




50




N

N

O

NR

Ra 2-OHb

36

36

4-OH 3-OMe

Figure 33

N

HC O

C

O

O

V NN

NN


38

=

Figure 34

NH

O

N NH H HH H HH H H

xxxxivii

R1 R1

R2

R2

R3

R3

4-NO2C6H4

2-NO2C6H4

34-(OH)2C6H3

39

39 R4

R4

Figure 35



better than IC50


50

(29114 plusmn 253120583M) [54]

3 Conclusion



References






































































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of


OH

R

R171715151410

866552

Rabcdef

ghijkl

15

15 15CH3

CH3

CH3

CH3

C2H5

C2H5

C2H5

C2H5

C2H5

C2H5

CH3

C2H5

n n

N(CH2)nCH3

Figure 15

N16

CON1HN2H2

Figure 16

N

xv H

17

17

CONHN=CR1R2

R1 R2


Figure 17

N

N

O

R

NH

O

N N

OR


h BrBrBrBrBrBrBr

ijklmn

R

18

18 18R1 R1

R1

CH2CH3

C3H7

-CH2CH=CH2

-CH2C6H5CH3

CH3

C2H5

H

OH

C3H7

-CH2CH=CH2

-CH2C6H5

CH3

C2H5

Figure 18



abcdef

NN

OH

OHOH

OH

19

19R1

R1

R1

R2

R2 R2

R3

R3

R3

R4

R4

R4

R5

R5

R5

NO2

NO2

NO2

Figure 19


N

O

NH

N

Ar

abcdef

Rghijk

R

20

20 202-OHC6H5

4-OHC6H5

4-ClC6H4

4-NO2C6H5

2-NO2C6H4

4-FC6H4

4-OCH3C6H4


4-(CH3)2NC6H4

4-OH 3-OHCH3C6H3

Figure 20

N OO

CONHN C


21

21 21

R1

R1 R2 R1 R2

R2

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

3-NO2

4-CH3

4-NO2

4-OCH3

2-NO2

24-(Cl)2

34(OCH3)2

2-OH OCH3

Figure 21










NH

N

N N

N N

HN

Cl

Cl

O

O

-H-Cl

12

22

22

R1

R1

R1

Figure 22

N

NI

O

CH

NHN C

S

F

23

NH2

Figure 23

N

HN

N

N

ON

S

R

a Hbc

R

24

24

N+

minusO

CH3

CH3

CH3

H3COCH3

Figure 24

NN

N

O

f H OH OH H H

25

25 R1 R2 R3 R4 R5

R1

R2

R3

R4

R4

CH3H3C

Figure 25


Cl Cl

NH

26

CHONH=CHAr

Figure 26

N

N N

O

N

NN

SHF

O

N

R


j 4-Fekf

R

27

27 27

4-CH3O

2-CH3O34-OCH2O

345-(CH3O)3 4-NO2


Figure 27



2 TNF-120572 and






2was




CH

N NH

O

d OH H H

CHN

O CuO N

HN O

NH

CHO

2829

2829

OC2H5

R1

R1

R2

R2

R2

R3

R3

R3

R3

R3

R4

R4

R4

R4

CH3

Figure 28

N

N

NO

RSH

N

NH

N


30

30 R1

R1

Figure 29







50) value of 33








abcdef

ghijklmn

Ar ArO

HN

N Ar

31

31 312-OHC6H4

4-NO2C6H4

4-NO2C6H4

4-CH3C6H4

4-CH3C6H4

2-OHC10H6

3-NO2C6H4

-C6H4

4-ClC6H4

R998400

R998400 R998400

2-OHC6H4

4-OHC6H4

2-NO2C6H4

2-COC6H5

2-COC6H5

2-COC6H5

2-COC6H5

2-COC6H5

2-COC6H5

2-COC6H5

2-COC6H5

3-OCH3 4-OHC6H3

3-OCH3 4-OHC6H3

Figure 30

N

NN

RO

RH 2-OHHHH

4-ClH H

H 4-OHH

4-OHH 4-ClHH

ghijkl

abcdef

R R

2-NO2

4-OCH3


2-OCH3

R998400 R998400

34

34 34

CH3

CH3

CH3

Figure 31

O

Cl Cl N=HC

R H2-OH4-OH

4-Cl

abcdefghi

R

4-NO2

4-OCH3

345-(OCH3)3

4-OH 3-OCH3

-CH=CH-C6H535

35

Figure 32




50




N

N

O

NR

Ra 2-OHb

36

36

4-OH 3-OMe

Figure 33

N

HC O

C

O

O

V NN

NN


38

=

Figure 34

NH

O

N NH H HH H HH H H

xxxxivii

R1 R1

R2

R2

R3

R3

4-NO2C6H4

2-NO2C6H4

34-(OH)2C6H3

39

39 R4

R4

Figure 35



better than IC50


50

(29114 plusmn 253120583M) [54]

3 Conclusion



References






































































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of


N

O

NH

N

Ar

abcdef

Rghijk

R

20

20 202-OHC6H5

4-OHC6H5

4-ClC6H4

4-NO2C6H5

2-NO2C6H4

4-FC6H4

4-OCH3C6H4


4-(CH3)2NC6H4

4-OH 3-OHCH3C6H3

Figure 20

N OO

CONHN C


21

21 21

R1

R1 R2 R1 R2

R2

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

3-NO2

4-CH3

4-NO2

4-OCH3

2-NO2

24-(Cl)2

34(OCH3)2

2-OH OCH3

Figure 21










NH

N

N N

N N

HN

Cl

Cl

O

O

-H-Cl

12

22

22

R1

R1

R1

Figure 22

N

NI

O

CH

NHN C

S

F

23

NH2

Figure 23

N

HN

N

N

ON

S

R

a Hbc

R

24

24

N+

minusO

CH3

CH3

CH3

H3COCH3

Figure 24

NN

N

O

f H OH OH H H

25

25 R1 R2 R3 R4 R5

R1

R2

R3

R4

R4

CH3H3C

Figure 25


Cl Cl

NH

26

CHONH=CHAr

Figure 26

N

N N

O

N

NN

SHF

O

N

R


j 4-Fekf

R

27

27 27

4-CH3O

2-CH3O34-OCH2O

345-(CH3O)3 4-NO2


Figure 27



2 TNF-120572 and






2was




CH

N NH

O

d OH H H

CHN

O CuO N

HN O

NH

CHO

2829

2829

OC2H5

R1

R1

R2

R2

R2

R3

R3

R3

R3

R3

R4

R4

R4

R4

CH3

Figure 28

N

N

NO

RSH

N

NH

N


30

30 R1

R1

Figure 29







50) value of 33








abcdef

ghijklmn

Ar ArO

HN

N Ar

31

31 312-OHC6H4

4-NO2C6H4

4-NO2C6H4

4-CH3C6H4

4-CH3C6H4

2-OHC10H6

3-NO2C6H4

-C6H4

4-ClC6H4

R998400

R998400 R998400

2-OHC6H4

4-OHC6H4

2-NO2C6H4

2-COC6H5

2-COC6H5

2-COC6H5

2-COC6H5

2-COC6H5

2-COC6H5

2-COC6H5

2-COC6H5

3-OCH3 4-OHC6H3

3-OCH3 4-OHC6H3

Figure 30

N

NN

RO

RH 2-OHHHH

4-ClH H

H 4-OHH

4-OHH 4-ClHH

ghijkl

abcdef

R R

2-NO2

4-OCH3


2-OCH3

R998400 R998400

34

34 34

CH3

CH3

CH3

Figure 31

O

Cl Cl N=HC

R H2-OH4-OH

4-Cl

abcdefghi

R

4-NO2

4-OCH3

345-(OCH3)3

4-OH 3-OCH3

-CH=CH-C6H535

35

Figure 32




50




N

N

O

NR

Ra 2-OHb

36

36

4-OH 3-OMe

Figure 33

N

HC O

C

O

O

V NN

NN


38

=

Figure 34

NH

O

N NH H HH H HH H H

xxxxivii

R1 R1

R2

R2

R3

R3

4-NO2C6H4

2-NO2C6H4

34-(OH)2C6H3

39

39 R4

R4

Figure 35



better than IC50


50

(29114 plusmn 253120583M) [54]

3 Conclusion



References






































































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of


NH

N

N N

N N

HN

Cl

Cl

O

O

-H-Cl

12

22

22

R1

R1

R1

Figure 22

N

NI

O

CH

NHN C

S

F

23

NH2

Figure 23

N

HN

N

N

ON

S

R

a Hbc

R

24

24

N+

minusO

CH3

CH3

CH3

H3COCH3

Figure 24

NN

N

O

f H OH OH H H

25

25 R1 R2 R3 R4 R5

R1

R2

R3

R4

R4

CH3H3C

Figure 25


Cl Cl

NH

26

CHONH=CHAr

Figure 26

N

N N

O

N

NN

SHF

O

N

R


j 4-Fekf

R

27

27 27

4-CH3O

2-CH3O34-OCH2O

345-(CH3O)3 4-NO2


Figure 27



2 TNF-120572 and






2was




CH

N NH

O

d OH H H

CHN

O CuO N

HN O

NH

CHO

2829

2829

OC2H5

R1

R1

R2

R2

R2

R3

R3

R3

R3

R3

R4

R4

R4

R4

CH3

Figure 28

N

N

NO

RSH

N

NH

N


30

30 R1

R1

Figure 29







50) value of 33








abcdef

ghijklmn

Ar ArO

HN

N Ar

31

31 312-OHC6H4

4-NO2C6H4

4-NO2C6H4

4-CH3C6H4

4-CH3C6H4

2-OHC10H6

3-NO2C6H4

-C6H4

4-ClC6H4

R998400

R998400 R998400

2-OHC6H4

4-OHC6H4

2-NO2C6H4

2-COC6H5

2-COC6H5

2-COC6H5

2-COC6H5

2-COC6H5

2-COC6H5

2-COC6H5

2-COC6H5

3-OCH3 4-OHC6H3

3-OCH3 4-OHC6H3

Figure 30

N

NN

RO

RH 2-OHHHH

4-ClH H

H 4-OHH

4-OHH 4-ClHH

ghijkl

abcdef

R R

2-NO2

4-OCH3


2-OCH3

R998400 R998400

34

34 34

CH3

CH3

CH3

Figure 31

O

Cl Cl N=HC

R H2-OH4-OH

4-Cl

abcdefghi

R

4-NO2

4-OCH3

345-(OCH3)3

4-OH 3-OCH3

-CH=CH-C6H535

35

Figure 32




50




N

N

O

NR

Ra 2-OHb

36

36

4-OH 3-OMe

Figure 33

N

HC O

C

O

O

V NN

NN


38

=

Figure 34

NH

O

N NH H HH H HH H H

xxxxivii

R1 R1

R2

R2

R3

R3

4-NO2C6H4

2-NO2C6H4

34-(OH)2C6H3

39

39 R4

R4

Figure 35



better than IC50


50

(29114 plusmn 253120583M) [54]

3 Conclusion



References






































































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of


Cl Cl

NH

26

CHONH=CHAr

Figure 26

N

N N

O

N

NN

SHF

O

N

R


j 4-Fekf

R

27

27 27

4-CH3O

2-CH3O34-OCH2O

345-(CH3O)3 4-NO2


Figure 27



2 TNF-120572 and






2was




CH

N NH

O

d OH H H

CHN

O CuO N

HN O

NH

CHO

2829

2829

OC2H5

R1

R1

R2

R2

R2

R3

R3

R3

R3

R3

R4

R4

R4

R4

CH3

Figure 28

N

N

NO

RSH

N

NH

N


30

30 R1

R1

Figure 29







50) value of 33








abcdef

ghijklmn

Ar ArO

HN

N Ar

31

31 312-OHC6H4

4-NO2C6H4

4-NO2C6H4

4-CH3C6H4

4-CH3C6H4

2-OHC10H6

3-NO2C6H4

-C6H4

4-ClC6H4

R998400

R998400 R998400

2-OHC6H4

4-OHC6H4

2-NO2C6H4

2-COC6H5

2-COC6H5

2-COC6H5

2-COC6H5

2-COC6H5

2-COC6H5

2-COC6H5

2-COC6H5

3-OCH3 4-OHC6H3

3-OCH3 4-OHC6H3

Figure 30

N

NN

RO

RH 2-OHHHH

4-ClH H

H 4-OHH

4-OHH 4-ClHH

ghijkl

abcdef

R R

2-NO2

4-OCH3


2-OCH3

R998400 R998400

34

34 34

CH3

CH3

CH3

Figure 31

O

Cl Cl N=HC

R H2-OH4-OH

4-Cl

abcdefghi

R

4-NO2

4-OCH3

345-(OCH3)3

4-OH 3-OCH3

-CH=CH-C6H535

35

Figure 32




50




N

N

O

NR

Ra 2-OHb

36

36

4-OH 3-OMe

Figure 33

N

HC O

C

O

O

V NN

NN


38

=

Figure 34

NH

O

N NH H HH H HH H H

xxxxivii

R1 R1

R2

R2

R3

R3

4-NO2C6H4

2-NO2C6H4

34-(OH)2C6H3

39

39 R4

R4

Figure 35



better than IC50


50

(29114 plusmn 253120583M) [54]

3 Conclusion



References






































































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of


CH

N NH

O

d OH H H

CHN

O CuO N

HN O

NH

CHO

2829

2829

OC2H5

R1

R1

R2

R2

R2

R3

R3

R3

R3

R3

R4

R4

R4

R4

CH3

Figure 28

N

N

NO

RSH

N

NH

N


30

30 R1

R1

Figure 29







50) value of 33








abcdef

ghijklmn

Ar ArO

HN

N Ar

31

31 312-OHC6H4

4-NO2C6H4

4-NO2C6H4

4-CH3C6H4

4-CH3C6H4

2-OHC10H6

3-NO2C6H4

-C6H4

4-ClC6H4

R998400

R998400 R998400

2-OHC6H4

4-OHC6H4

2-NO2C6H4

2-COC6H5

2-COC6H5

2-COC6H5

2-COC6H5

2-COC6H5

2-COC6H5

2-COC6H5

2-COC6H5

3-OCH3 4-OHC6H3

3-OCH3 4-OHC6H3

Figure 30

N

NN

RO

RH 2-OHHHH

4-ClH H

H 4-OHH

4-OHH 4-ClHH

ghijkl

abcdef

R R

2-NO2

4-OCH3


2-OCH3

R998400 R998400

34

34 34

CH3

CH3

CH3

Figure 31

O

Cl Cl N=HC

R H2-OH4-OH

4-Cl

abcdefghi

R

4-NO2

4-OCH3

345-(OCH3)3

4-OH 3-OCH3

-CH=CH-C6H535

35

Figure 32




50




N

N

O

NR

Ra 2-OHb

36

36

4-OH 3-OMe

Figure 33

N

HC O

C

O

O

V NN

NN


38

=

Figure 34

NH

O

N NH H HH H HH H H

xxxxivii

R1 R1

R2

R2

R3

R3

4-NO2C6H4

2-NO2C6H4

34-(OH)2C6H3

39

39 R4

R4

Figure 35



better than IC50


50

(29114 plusmn 253120583M) [54]

3 Conclusion



References






































































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of



abcdef

ghijklmn

Ar ArO

HN

N Ar

31

31 312-OHC6H4

4-NO2C6H4

4-NO2C6H4

4-CH3C6H4

4-CH3C6H4

2-OHC10H6

3-NO2C6H4

-C6H4

4-ClC6H4

R998400

R998400 R998400

2-OHC6H4

4-OHC6H4

2-NO2C6H4

2-COC6H5

2-COC6H5

2-COC6H5

2-COC6H5

2-COC6H5

2-COC6H5

2-COC6H5

2-COC6H5

3-OCH3 4-OHC6H3

3-OCH3 4-OHC6H3

Figure 30

N

NN

RO

RH 2-OHHHH

4-ClH H

H 4-OHH

4-OHH 4-ClHH

ghijkl

abcdef

R R

2-NO2

4-OCH3


2-OCH3

R998400 R998400

34

34 34

CH3

CH3

CH3

Figure 31

O

Cl Cl N=HC

R H2-OH4-OH

4-Cl

abcdefghi

R

4-NO2

4-OCH3

345-(OCH3)3

4-OH 3-OCH3

-CH=CH-C6H535

35

Figure 32




50




N

N

O

NR

Ra 2-OHb

36

36

4-OH 3-OMe

Figure 33

N

HC O

C

O

O

V NN

NN


38

=

Figure 34

NH

O

N NH H HH H HH H H

xxxxivii

R1 R1

R2

R2

R3

R3

4-NO2C6H4

2-NO2C6H4

34-(OH)2C6H3

39

39 R4

R4

Figure 35



better than IC50


50

(29114 plusmn 253120583M) [54]

3 Conclusion



References






































































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of


N

N

O

NR

Ra 2-OHb

36

36

4-OH 3-OMe

Figure 33

N

HC O

C

O

O

V NN

NN


38

=

Figure 34

NH

O

N NH H HH H HH H H

xxxxivii

R1 R1

R2

R2

R3

R3

4-NO2C6H4

2-NO2C6H4

34-(OH)2C6H3

39

39 R4

R4

Figure 35



better than IC50


50

(29114 plusmn 253120583M) [54]

3 Conclusion



References






































































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of



































































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of

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