PHYTOCHEMICAL AND BIOLOGICAL STUDmS ON GONIOTHALAMUS TAPIS

Siddiq Hafiz Hassan

Bachelor of Science with Honours (Resource CbelIlistry)

2006

I"uSlt Khidml' MI1Jumat Akalk>mlk lJI'IIlYJ.~~T1 ~'" I yq... S1\ IfAWAJ<

PHYTOCHEMICAL AND BIOLOGICAL STlJDIES ON

GONIOTHALAMUS TAPIS

SlDDIQ HAFIZ HASSAN

This project is submitted in panial fulfillment of th e requirements for the degree of Bachelor of Science with Honours (Resource Chemistry)

Faculty of Resource Science and Technology UN IVERS ITI MALA YS IA SARA WAK

2006

..... .--- ----- .-

DECLARATIO

No ponion of the work refened to in this di ssel1a tion has been submitted in sUppO!1 of an

appli cation for another degree of qualification of this or any other university or institution

ofhigher lea ming.

Program 0 f Resource Chemistry

Faculty of Resource Science and Technology

Uni versiti Mala ys ia Sarawak

III

.---- ---- .

ACKNOWLEDGEMENT

First o f all , [ wo uld like to take this opportunity to express my heaniest gratitude to my

superv iso r, Assoc. Prof. Dr. Fasihuddin Ahmad [or her gu ida nce and support in helping

me to carry out this final year project.

I wo uld also like to thank Assoc. Pro f. Dr. Zaini Ass im and Mr. Rajuna Tahir for their

kind ass istance especially during the operation o f equipment s and mac hines in the

laboratOly.

Besides, I wo uld like to convey my warmest and s incere thanks to all my fri ends and

anyone who has in o ne way or another contributed to wards the improvement and success

of this fin a l yea r project.

Last but not leas t, my appreciation also goes up to my fa mil y for [heu· endless suppOl1

thro ughout the proj ect.

IV

"us.t Kbidmal MakJumlt Ahdrllljj. UNJVEltSm . 1AL'IYSIA S\RAWAJ(

TABLE OF CONTENTS

DECLARAnON iii

ACKNOWLEDGEMENT iv

TABLE OF CONTENTS v

LIST OF TABLES viii

LIST OF APPENDIXES ix

ABSTRACT xii

A BSTRAK xiii

CHAPTER I: INTRODUCTION 1

1.1 Natural Products I

1.1.1 Primary Metabolites 2

1.1.2 Secondary Metabolites 2

1.2 Annonaceae 3

1.3 Goniolhalallllls 7

v

.­

1.3.1 Dist ribu tion 7

1.3.2 Features 9

1.3.3 Significances 10

1.3.4 Phytochemical and Biological Studies 11

1.4 GOniOlllalalllllS lapis 15

1.4.1 Features 15

1.4.2 Distribution and Habitat 16

1.4.3 Significances 16

1.5 Objective 16

CHAPTER 2: MATERIALS AND METHODS 17

2.1 Plant Matcrial 17

2.2 General Expcrimental Procedures 17

2.3 Extraction 18

2.4 Isolation and Purification 18

2.4.1 Thin Layer Chromatography (TLC) 18

2.4.2 Column Chromatography (CC) 19

2.5 PII rity Determination 19

2.5.1 Gas Chromatography-Flame Ionization Detector (GCFID) 19

2.6 Structural Elucidation 20

2.6.1 Fourier Transform Infrared (FTIR) Spectrometer 20

2.6.2 Gas Chromatography-Mass Spectroscopy (GC-MS) 20

2.7 Brine Shrimp Toxicity Test 21

Vi

~------ .

22 CHA PTER 3: RESULTS AND DISCUSSIONS

3.1 Extraction 22

3.2 Isolation and Purification 23

3.2.1 Thin Layer Chromatography (TLC) 23

3.2.1.1 Hexane Partition 23

3.2.1.2 Dichloromethane Partition 24

3.2.1.3 Ethyl Acetate Partition 25

3.2.2 Column Ch romatography (CC) 25

3.2.2.1 Hexane Partition 26

3.2.2.2 Dichloromethane Par1ition 29

3.2.2.3 Ethyl Acetate Partition 31

3.3 Purity Determination 32

3.3.1 Gas Chromatography-Flame Ionization Detector (GC-FID) 32

3.4 Structu rc Elucidation 33

3.4.1 Fourier Transform Infrared (FTIR) Spectrometer 33

3.4.2 Gas Chromatography-Mass Spectroscopy (GC-MS) 35

3.5 Brine Shrimp Tox.icity Test 37

CHAPTER 4: CONCLUSION AND SUGGESTIONS 39

BIBLlOGRAPHY 41

APPENDIXES

V II

. -- --- ~.-

-- ---

LIST OF TABLES

Pa ges

Table 1.1 : T he dis tribution of Coniolhalamlls spec ies in Malaysia (Din , 2000) . 8

Table 1.2 : T he medic inal uses of some Goniolholamlls species. 11

Table 1.3 : Secondary metabo lites reported fi'o m so me GO l1io[halamlls 14

species and their biological activiti es.

Table 3.1 : The weights and percentage yield s o fpar1itions on methanol 23

extract o r c. lapis.

Table 3.2 : Rr values fo r hexane pal1ition fi 'om C. lapis extract deve loped 24

in hexa ne-dichloro methane ( 15: I) solvent system.

Table 3.3 : Rrvalues for dichloro methane pal1ition from C. lapis extract 24

developed in hexane-dichloromethane (I :25) so lvent system.

Table 3.4 : R,-values for ethyl acetate partition fi'o m G. lapis extract 25

developed in dic hloromethane-ethy l acetate ( 12: I) so lvC'n t system.

Table 3.5 : The phys ical appearances, so lvents systems and weights [or 27

combined 6'<1c tio ns iso lated by co lumn chro matography for

hexane partition.

Table 3.6 : The phys ical appearances, solvents systems and weights for 30

combined 6'ac tions isolated by co lunm chromatography

for dic hloromethane partition.

Table 3.7 : The physica l appea rances, so lvents systems and weight s for 32

combined fract ions iso la ted by co lumn chromatography for ethyl

aceta te partition.

Ylll

_ "

Table 3.8 : The types 0 f functiona l groups present in TH21 , T H26, TH49 34

and TO 13 based on the infi'ared spectra .

Table 3.9 : The average number o f deaths of Ar/emia salil1a as a fu nction 0 f 38

concentr ations and contact times for the bark a r G. lap is .

IX

- .-------- ..

- -

LIST OF APPENDIXES

Appendix I : Hexa ne partition in hexa ne-dichloromethane ( 151 ).

Appendix 2 : Oichloromethane paI1ition in hexane-dichloromethane ( I :25).

Appendix 3 : Ethyl acetate paI1ition in dichloromethane-ethyl acetate (12:1).

Appendix 4 : Hexa ne paI1itions (fi'actions 1-162) in suit able so lve nt systems.

Appendix 5 : Oichloromcthane-combined fractions (fi'ac tions 1-70) U1 suitable solvent

sys tems.

Appendix 6 : Ethyl aceta te combined-frac tions (fi'ac tio ns 1-27 ) in ethyl acetate.

Appendix 7 : Chromatogram fo r hexa ne-combined fractio n, TH21 at retenti o n

time 2 1.6 min .

Appendix 8 : Chro matog ram fo r hexane-co mbined fi'action , TH26 at retention

time 22.2 min.

Appendix 9 : Chromatogram for hexane-combined fract ion, TH49 at retention

time 15. 3 min.

Appendix 10 : Clu'o matogram for dichloromethane-combined fractio n, TO l3 at

retention time 22.2 min.

Appendix 11 : Infrared spectrum lo r hexa ne-co mbined fraction, TH2 1.

Appendb: 12 : Infj'ared spec trum for hexa ne-combined fj'actio n, TH26.

Appendix 13 : Infi'ared spectrum fo r hexa ne-co mbined fj'action, TH49.

Appendix 14 : In frared spectrum fo r dichloromethane-combined fraction , TD I3.

Appendix 15 : Mass spec trum for hexane-combin ed fi'action, TH21 at retention time

16.3 min.

x

---------- ..

A ppendix 16 : Mass spectrum for hexane-combined ii'action, TH26 at retention time

16.3 min .

A ppendix 17 : Mass spectrum for hexane-combined fi·action. TH49 at retention time

15.3 min.

Appendix 18 : Mass spectrum Cor dichloromethane-combined fj-action. TO 13 at

retention time 16 .3 min.

XI

.-. -~-- - ..-

ABSTRACT

Phytochemical and biological studies have been calTi ed o ut on the ext rac t ob tamed from

the stem bark 0 f GoniOlholamus lapis. Extractio n using methanol affo rd ed dark brown

extract of 193.64 g ( 13 .83 %). Solvent panitio n was carri ed o ut using so lvents with

inc reas ing polarit y namel y, hexane, dichloromethane and e thyl acetate. Iso lation and

purificatio n were performed using colunm chromatography. One pure compo und and

o ne semi pure compound with the molecular mass of 200 g/mo l and 222 g/mol

cOlTesponding to molecular formula ofC'3H'202 and C 'SH260 respectively were isolated.

Compound wi th molecular mass of200 was isolated as yellow crys tal with melting point

of72.9-73 .1 D'C with Rr value of 0.36 in chloroform-ethyl acetate (I :4). Infrared spectrum

revealed s trong abso lption band at frequency of 17 18 c m'! that was asc ribed to a C~O

ketones (acycl ic). The medium absorption at 145 1 C lll" mdicated tha t th e presence of

c=c conjugated bond m aro matic co mpound , while the strong absorp tio n a t 1243 cm'!

indica ted that the presence o f c-o bond (ethers). Based o n the mass spec trum, melting

point , mfonnation fi'o m infrared and comparison w ith published data , the pure compound

has been identified as goniothalamm. Second compound exhibited the Rrvalue of 0.80 in

chloroform-et hyl acetat e (4: I). Comparison made with the mass spectll.!m, 'nformation

fi'om infrared and published data suggested this compo und mo", probably is {3--eudesmol.

The brine shrimp toxic it y test showed that none of the extract and patiitions were toxic to

the larvae ofAnemia sa lina.

Keywords : Goniolhalumus topis, chromatography, spectroscopy, goniothalamin,

~-eudesmo l , brine shrimp to xic ity tes t

xu

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- -- - ------- ..

A BSTRAK

Kajianjitokimia dan bi%gi le/ah dija/ankan ke a/as eks trak kulit batang Goniolha/amus

taois. Proses pengeks trakan le/ah cli/akukan dengan menggllnakan metano/ bagi

memberikan sebanyak 193.64 g (13.83 %) ekstrak berv..'arna perang kehitaman.

Pemfraksian Ie/ail di/akukan clengan menggllnakall p e /al1lt dellgan pertambahan

kepo/aran iaitu heksana, dik/orometanu dan eti/ aselal. Pemisahan dan penu/enan le/ah

cli/akukan ke alas semua partis i menggllnakan kromalOgraji tllntS. Salll sebation Ill/en

dan salll sebalian separa lu/en dengan j isim mo/ekll/ 200 glmo/ and 222 glmo/ yang

berseslla ian dengan jormll/a mole/wi CfJH U 0 2 dan C/sH2~O masing-masingnya te/ah

be/jaya dipisahkan . Sebalian til/en dengall jisim mo/eku/ 200 glmo/ dipero/ehi sebagai

hab/llr kilning dengan taka t /ebur 72.9-73./C dan memberikan ni/oi R, 0.36 do/am

pe/amt k/oro(orm-eti/ aselot (1:4). Spekll1lln inframerah menul1jukkal1 penyaapan kual

pacla jiekuensi 1718 em-/ menunjukkan kehodiran ikatcJn C=O ke toJ1 (asiklik).

Penyerapan sederhana pada /iekZlensi /451 cm-/ menZlnj llki<on kehadiran ikatan C=C

(aromatik). Penyerapon kllat pada /iekuensi 1243 cm-/ menlln jllkkan kehadiran ikatan

C-O eler. Be rdasarkan mak/umat spektroskopi, takal /ebllr, infi 'al11erah dan daw yang

pemah diterhilkan , sebatilll1 lersebut te/ah dikena/pas li sebagai goniota/amin. Sebatian

kedua memberikaJ1 ni/ai R j 0.80 da/am pe/anll k/orojorm-eli/ asetat (4: 1). BelL/aswkan

mak/umo! spektJ'Oskopi, infiw1(crah dan data yang pemah diterbi tkaJ1 , sebalian terseiJut

berkemungkiJ1an besw' ada/aIJ {3--eudesl11ol. Ujian ketoksikon ke alas anak udang

mellunjukkaJ1 ekso'ak dan sel11ua partisi tidak {oksik teF/wdap /(JIVG Anemia, salinq.

Kafakllllci . Gonioliw/amlls tapis krOl11alagraji, speklJ'Oskopi, goniow /arnill,

{3--eudesmol, IIj ian kelOksikan anok udang

XUl

=-~ _00__ _ -_____

CHAPTER 1: INTRODUCTION

1.1 Natural Products

Early records of the medic inal uses of natural products have been found in

Babylo nian wri t ings, among Egyptians documents and in the ancient cultura l reco rds 0 f

Asia panicularly in China and India. In Westem cultures, the study o f natural products

(vegetables, animal and minerals) used in medicine was carried during the Greek and

Roman empires and survives today in almost all modern countries. Drug like aspirins,

henbane, mandrake (hyoscyamine) and ginseng are well over 6000 years o ld . The lise of

crud e natural products in medicine still commonplace throughout Europe, A5'ica and

Asia (Oliver-Bever, 1986).

The study of natural products can now be more readily targeted at the end­

prod ucts with conunerciaJ implications. Natural products and their int erac tions with

other biomo leculcs are at the cent er of life sciences initiative in many co untries. All over

the wo rld there has been the search for molecular and genetic biodivers it y fo r material s

and pharmaceutica ls. The molecular diversit y products o f terrestri al and marine origins

continue to confo und and exceed those deri ved 5'001 co mbinatoria l synthet ic chemistry.

The evo lutionary origin 0 f natural products e nsures that they function in co mp lex

biological-mo lecular mechani sms in the s tlllggle of existence of organisms. The study 0 f

bioactive natural products constitutes the lirst step in drug discovery programmes whil e

the eventual outcome of blockbuster drugs may not be that easily realized in view of high

cost and research eflo l1. However in the past decade, there has been a parad igm shift in

recognizing the role of phytochemicals in the development of nlltracelltica ls,

_...--.-.------- 1 •

-- --

cosmeceuticals and OTe supplements/medicines (Goh el 01., 2000). In ge neral, natural

products can be c lassified into two major groups which are primary and seco ndary

metabo lites (Seig ler, 1998).

1.1.1 Primary Metabolites

Ptimary metabolites are those produced by and in vo lved in prim ary and metabo lic

processes such as respiration and photosynthesis. T hese inc lude ubiqu itous small

molecules such as sugars, amino acids, tri-carboxylic acids or Krcbs cyc les intelmediates ,

nucleic ac ids and polysaccharides. Many sugars, protei.n amino ac ids, low -molec ul ar­

weights organic acids, fatty acids and some proteins are id entical in animals, bacteria,

li.lI1gi, plants and other organisms. Nonetheless, differences in the p athw ays leading to

these primary metabolites and the actual compounds involved in somc fund amental

processes differ in so me instances (Haslam, 1986).

1. 1.2 Secondary Metabolites

Seco ndary metabolites, produced by pathw ays deri ved fro m primary metabo lie

ro ut es, are numerous and w idespread espec ially in the higher plant s (Se ig ler, 1998). The

amount o f any plant secondary compound found in an o rgal11sm IS the result o f

equilibrium amo ng synthes is, s torage and degradation . Regulatio n o f seco ndary

metabo lit es is complex. The onset of secondary metabo li sm is linked to the

deve lopmental stage of the o rganism and is often close ly linked to morpholog ical and

cyt olog ical changes (Haslam, 1986).

2

~.

Genera ll y, the fo rmation o f prod ucts in seco nda ry metabo lis m appears to be

enzyme limited , but the level o f subst rates presents inOuences the prod uction o f o ther

secondary metabolites especia ll y in artific ial cu lture (Bu'Lock, 1980). Others ha ve

suggested secondary metabo lites once played a metabo lic role in the organism producing

them or those they were primary metabolit es in the past (Williams el aI., 1989). Many

compounds do lJave intermediate ro les between primary and secondary metabolism. For

instance, some plant secondary co mpounds such as gibberellins are assoc iated with plant

growth and deve lopment (Seigler, 1998).

Other secondary metabo lites serve as reserves of energy and as precurso rs o f

important organic compounds or so urces of nitrogen anel may be recycled within the

plants (Ahmad dan Raji, 1993) . Modified seconda ry metabolites have d ifferent solubility

and other physica l proper1 ies than the parental compo unds and may invo lved in transport

and accumulation mechanisms in plants (Wink, 1987). Nonetheless, there is little

ev idence to suppon the notion that most or all secondary metabo li tes once had pri mary

ro les. T he examples of import ant grou ps o f secondary metabo lites are a lkalo ids,

Oavo noids and stero ids (W ill iams el aI. , 1989).

1.2 Annonaceae

An nonaceae is a large fa mily of trees and shrubs, found mostly in tropical and

subtropica l reg io ns. There is wide botanical diversity wit hin this fam il y w hich contains

more than 130 genera and 2300 species (Ram irez and Haye, 1995; Ala li el 01., (9 99).

Plants of the Annonaceae are very impol1ant sources of ed ible 51.1i ts and mater ial for

perfumery. T hey are a lso used in fo lk med ic ine in vario us capacities, such as

3

antitumo ral, paras itic idal and antidiarrhoeal ag ents (Leboeu f el ai , 1982). From the

phytochemical vi ewpoint, plants from this famil y have been in vestigated intensively,

motiva ted initially by the iso lation o f numerous a l.ka loids suc h as o uregid io ne ( I ) from

Psellduvaria macrophylla and several of Anno naceo us acetogenins (Leboeuf el al., 1982;

Mahmood el 01 , 1986).

CHP

CHP

o

1

The di scovery of uvaricin (2), the firs t Anno naceo us acerogenins I]-om Uvaria

acclImina la as an in vivo active antile ukimia (P-388) agent, inv igorated w id e interest in

this famil y (Jo lad el ai , 1982). A total o f 350 Anno naceo us acetogenins have been

iso la ted so far from the Anno naceae, predominantly I]-o m the genera Allnona, Asimill(l,

Rollin ia, Uvaria and GoniOlhalamlis in the past two decades (A la Ii el 01., 1999) . The

common stru ctura l fea tures o f Annonaceous acetogenins are a termin a l y-Iactone ring and

a termin al a liphatic s id e chain connected with some oxygen bear ing mo ieties, such as

zero to three tetrahyrofuran (THF) andlor tetrahydrop yran (T HP) rin gs and several

hyd roxy l gro ups. Stru cturally, most of these long-chain fatty acid der ivat ives may be

classifred into tJu·ee majo r g roups: mono-THF, adjacent bis-THF, and no nadj ace nt bis­

THF classes. Several minor groups also present such as no nadj acent THF or THP,

4

-- ----------- .....

!'uut Kbidmlll Maklumat Alta~ml" IIJ'ilVERSm MALAYSI AI\AWAK

adjacent tris-T HF and others (Rupprecht et al., 1990; Zeng el ai. , 1996; Alali el ai.,

1999).

o o

OH

o

o

2

Annonaceous acetogenins have emerged as potentially promis ing antica ncer drugs

for mu1tidrug resistant (MDR) cancers (Oberlies el ai., 1997) Structura lly, they be long

to a series o f C-35/C-37 natura l products, derived liom C-32/C-34 lo ng -c ha in fa tt y ac ids

that are cova lently bo und w ith a 2-pro panol unit. Accumul ating d ata has demons tra ted

that Annonaceo us acetogenins ha ve antitumor, parasi tic idal, pes ti<: ida1, a ntimicro bial a nd

immunosuppressive activ ities (A lali el ai. , 1999). The c ytotoxicity of Anno naceo us

acetogenins is mediated, at least pat1l y, by the depletion of ATP leve ls via th~ inllibition

of the NADH-ubiquinone oxidoreductase (complex J) of the mitochondrial electron

transpol1 sys tem (Zafra-Po lo el ai., 1996). Furthennore, they also inhibit th e ubiquinone ­

linked NADH oxidase that is constitutively expressed in the ce ll membrane of cancer

ce ils, but on ly transiently expressed in normal cells (MOlTe el ai., 1995).

5

------ -,.

.- ~

Mono-THF compounds are the largest group among the Anno naceo us

acetogenins (A la li el aI., 1999). Annonacin, a cytotox ic acetogenin co nt aining a mono­

THF ring wit h two flanking hydrox yls, has been isolated from plants of vario us ge nera

including Annona , Asimina, Goniotha/aI11L1s, Rollinia, Vvaria and Xy/opia (McCloud el

aI., 1987). It has been repol1ed to exeI1 its cytotoxic activity part ly by working as a DNA

topoiso merase I poison (Lopez el aI. , 200 I). Woo et af. (1995) found that murisol in A

and 16, 19-cis -murisolin iso lated from the seeds of Asil11ina tri/aba exhibited potent and

selective cytotoxicities on six human tumor cell lines. Meanwhile , Ahamadsahib et of.

(1993) isolated bullatacin (3) 11'om Annona bul/ata, which showed an in vivo activity 300

times stronger than that oftaxol against L1210 murine leukemia.

o o OH

~ OH

o

o

OH

3

6

-------- - .~,

1.3 Goniothalamus

1.3.1 Distrihu lion

GOlliolhaialJ1L1s is onc of the largest genera o f p alaeo tropica l Annonaceac, wit h

over 120 species widely distributed tlu'o ughout u'opical South- East Asia; the center of

diversi ty lies in Indochina and Western Malesia (S umatera , Peninsular Malays ia and

Borneo (Sa unders, 2002). About 44 species o f the gen us are found in Peninsular

Malaysia, Sabah and Sarawak. TabJe I.! shows the distribution of Goniothaiamus

species in Malays ia (D in, 2000).

7

- -

Table 1.1: The distribution of Coniothalamus species in Malaysia (Din, 2000).

Species

C. andersonii

C. i:>orneensis

G braeteosus

G caleareus

C. calyeinus

C. clemensii

C. crockerensis

C. curtisii

G cylindrOSligma

G doliehow/pus

CJaseiculallls

Gji.ilvus

C. giganteus

G giganlijolius

C. hoillumii

C. kinahaluensis

C. lo ng is lipi les

C. mauophylilis

G malayal7{,{s

G marcanii

G. montanus

G nilidus

C. poml/e/ivenius

G. PIlJlCliculi/iI/iUS

c. ridleyi

C. rosells

c. rosieI/o Ius

G rolllndisepalus

Borneo (Sabah and Sarawak)

End emic il1 Bomeo

Endemic in Bomeo

End emic in Sabah

End emic in Sarawak

Not found

Endemic in Sabah

End emic in Saba h

No t fo und

End emic in the south of Sarawak

End emic in Sarawak

Endemic in Bom80

N ot found

Not found

Endemic in Sabah

Not found

End emic in Saba h

Endemi c in Sarawak

Eas il y fo und

Easily found

Not found

Eas ily found

End emic in Sabah

End emic in Sarawak

Endemic in the east of Sabah

No t fo und

End emi c in Gunung Kinabalu

End emic in Saba h

No t found

Peninsular Malaysia

Not found

Not fo und

Not found

Not found

Eas ily fo und

Not fo und

Not fo und

End emic

No t found

Not found

No t found

Eas ily found

Eas ily found

Not found

Bukit Fraser

Not fo und

Not fo und

Easi ly found

Eas il y fo und

End emIc

Eas il y found

Not found

Not found

Not fo und

Eas il y fo und

No t fou nd

No t fou nd

Endemic

8

-------- - ~,. .

Table 1.1 : (continued).

Species Borneo (Sabah and Sarawak) Peninsular Malaysia

G. rufus Easily fo und Eas il y found

G. scorlechinii No t lound Easily found

G. sinclairianlls Endemic in Sarawak Not found

G. slenopelaius Endemic in Gunung Kinabalu Not fou nd

G. slenophyiius Endemic in Sarawak Not found

G. subevenius Not found End em ic

G. tapisoides Endemic in S araw ak Not found

G. tavoyen.sis Not found End emic

G. tel1l lifo lius Not found Easily lound

C. IOrtilipetaius Not found Easily found

G. umbrosus Not found Endemic

G. unduiatus Not found End emic

G. uvaroides Easil y lound Eas il y found

G. veiutinus End emic in Bomeo No t fo und

G. woodii Endemic in Bomeo Not found

G. wrayi NO! found Eas il y found

1.3.2 Features

The genus is characterized by axillary (or slight ly supraxillary) flowers that are

generally pendent. As with most Annonaceae, the flowers have three sepals and two

whor ls of three petals. T he outer petals are connivent over the rep rod uctive organs,

forming a distinctive mitrilorm dome. The flowers are bisexual , with numero us liee

stamens and carpels. The stamens have broad apical eormec tiveness that are variable in

shape, ranging fro m truncate to apiculate, and thecae that are septate; the po ll en is

released as tetrads. The apocarpus fi'uits are taxonomica ll y very impol1ant, with variation

in s ize, s hape, indument, peduncle and stripe length (Saunders. 2003).

9

1.3.3 Significances

A number of Co niolhalamlls spec ies are w ide ly emp loyed in folk medicines ,

alone o r as paI1 of herbal mixtures, as post-pal1um protective remedies, abol1ifacients,

insec t repell ent s and as a fiber sources (.Jewel's et ai., 1972; Perry. 1980; Goh el ai..

(995). Coniothalamus spec ies has been studied for th e iso lation and characterization of

bioactive const ituent s s ince more than a decad e by medicinal chemists due to their

proven use in folk medic ines for treatment o f various a ilment s. Local wo man takes dried

powdered leaves o f C. sesq/lipedalis gro wing in the hill y reg io ns of India during labor

pain and leaves a re used as mosq uito repe llent s by burning the plant (Ta lapatra el ai. ,

1985 ; Go h et 01., 1995). Ext ract from the seeds of C. a/11uyon have been used for the

treatm ent of edema and rheumatism (Kan, 1979).

Thi s genus is also widely used in traditional medicine by the loca l conununity in

Malaysia . For example, C . macrophyllus, C. malayan/lS and C. sco l"lechinii are often

used as abol1ifacients and post -natal treatment (Burkill, 1966). Decoctions of the leaves

o f C. /11a Cl"ophyllus can be used to treat co ld and fe ver (W ial1 , 2000). The roots of C

malayan"s have been used for the treatment o f rheumatis m and fe ver, whil e the barks are

used to treat meas les and as insect repe llent s (Mat Sa ll eh and Ahmad , 1989). In additio n,

G. tap's are w id e ly used as abol1ifac ients and to treat stomachache and diarrhea (LatiJJ,

1991; Wi al1 , 2000: Ahmad e l ai.. (995). The medic inal uses of some Go niothalamus

species are gi ven in Table I. 2.

10

Table 1.2: The med icina! uses of some Goniothalamus species.

Species Medicinal Use(s) Reference(s)

G. macJ'ophyl/us

G. malayanus

G. scortechinii

G. ses(jllipedalis

G. lapis

G. uvaroides

Fever,

abortifacient,

post-natal treatment

Fever,

abortifacient,

post-natal treatment

Abortifacient ,

post-natal treatment

Mosquito repellent,

post-natal treatment

Diarrhea,

abonitacient ,

stomachache

Abortifacient

Burki!! (1966); Wiart (2000)

Burkill (1966); Mat Sa lleh and

Ahmad (1989); Latiff (l991)

Burkill ( 1966)

Talaptra eL al. ( 1985); Goh el al.

( 1995 )

Latiff(1991) ; Wial1 (2000) ;

Ahmad el al. (1995)

Burkill (1 966)

1.3.4 Phytochemical and Biological Studies

Phytochemical studies and biological screenings on a number of GoniothalamliS

species have resulted in the isolation and characterization of various compo unds with a

variety of bio logical activity. These include Annonac eous acetogenins (Fang el al" 1992 ;

Gu et ai , 1994) , styry l- Iactones (Sam et ai , 1987; Hisham et ai , 2000), alkaloids

(Ta lapatra el al. , 1988 ; Zhang eL a I. , 1999) and fla vo noids (Talapat ra et al. , In5) .

Styryl-Iac tones o r styry l-p yrone derivatives (S PD) have been found to be

abundant in Goniothalamus spec ics which is co mmo nl y found in Ma lays ia (Jewers et aI. ,

1972). Previous studies o n S PD suggest this biologically acti ve compound as an

antipro lile rative and selecti ve cytotox ic agent. In vitro studies on SPD showed that this

II