synthesis, spectral characterization and bioactivity of novel

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  1. 1. SYNTHESIS, SPECTRAL CHARACTERIZATION AND BIOACTIVITY OF NOVEL ORGANOPHOSPHORUS COMPOUNDS DEPARTMENT OF BIOCHEMISTRY AND MICROBIOLOGY CANDIDATE: NEKHUMBE DIIMISENI EZEKIEL SUPERVISOR: Prof. AR Opoku Co-supervisor: Dr. C Sampath
  2. 2. INTRODUCTION TO ORGANOPHOSPHORUS COMPOUNDS Organophosphorus compounds are chemical compounds containing carbon-phosphorus bonds. Phosphorus-carbon bond formation has attracted much attention because of its application in organic synthesis and bioorganic chemistry. Organophosphorus compounds are mostly esters, amides or thiol derivatives of phosphonic acid and constitute a large group of chemical compounds.
  3. 3. APPLICATIONS VERTERINARY MEDICININE PHARMACEUTICALS AGRICULTURE - INSECTICIDES
  4. 4. INTRODUCTION TO ALPHA-HYDROXYPHOSPHONATES What are -Hydroxyphosphonates? - Hydroxyphosphonates are class of Organophosphorus compounds of synthetic interest because of their biological activity.
  5. 5. Their biological activities include: anti-cancer, anti-viral, anti- bacterial, anti-fungal, anti-leukemic and many other biological activities (Subba et al., 2012). They are useful precursors of - functionalized phosphonates such as:- -Aminophosphonates -Aminophosphonic acids Pudovik reaction (Pudovik, 1972) Kabachnik-Field reaction (Fields, 1952)
  6. 6. The two main routes for synthesis of -Hydroxyphosphonates Pudovik reaction Abramov reaction In the Abramov reaction, an aldehyde or a ketone is heated with trialkyl or dialkylphosphite to obtain alpha-Hydroxyphosphonates (Subba et al., 2012).
  7. 7. AIM OF THE CURRENT RESEARCH PROJECT To synthesize Novel -Hydroxyphosphonates compounds and test their antibacterial and anticancer activities.
  8. 8. OBJECTIVES OF THE PROJECT Design and synthesize eco-friendly novel -Hydroxyphosphonates having biological importance. Develop simple and effective method for synthesis of target molecules. Characterize the structure of the newly synthesized -Hydroxyphosphonates by elemental analysis, spectral techniques. Assess the antibacterial and anticancer activity of the synthesized compounds.
  9. 9. MATERIALS AND METHODS
  10. 10. RESULTS AND DISCUSSION . MP: 80-82oC
  11. 11. MP: 74-76oC
  12. 12. MP: 130-132oC
  13. 13. MP: 142-144oC
  14. 14. MP: 60-69oC
  15. 15. MP: 73-75oC
  16. 16. MP: 125-127oC
  17. 17. THIN LAYER CHROMATOGRAPHY (TLC) WASHING OF IMPURE SYNTHESIZED COMPOUNDS SPECTROSCOPIC STUDIES ANTIBACTERIAL ACTIVITY TLC Hexane Ethyl acetate ANTICANCER ACTIVITY EIGHT SYNTHESIZED COMPOUNDS
  18. 18. IR SPECTRA RESULTS FOR: COMPOUND 1
  19. 19. C P O OH H Cl Cl O O COMPOUND 8
  20. 20. O O C H OH P O O O COMPOUND 9
  21. 21. ANTIBACTERIAL ACTIVITY MICROBOTH DILUTION METHOD WAS USED TO TEST THE MINIMUM INHIBITORY CONCENTRATION AND MINIMUM BACTERICIDAL CONCENTRATION OF THE SYNTHESIZED COMPOUNDS
  22. 22. Staphylococcus aureas ATCC-25925 Bacillus cereus ATCC 10702 Vibrio fuvialis AL004 Escherichia coli ATCC 10819
  23. 23. MINIMUM INHIBITORY CONCENTRATION (MIC) Table 1: Antibacterial activities of 8 novel synthesized alpha-Hydroxyphosphonates. NOTE: ---- denotes the resistance towards the test antibacterial agent at a maximum test concentration of 5mg/ml. Microorganisms Synthesized compounds (alpha-Hydroxyphosphonates) Controls C1 C2 C3 C4 C5 C6 C7 C8 Ciprofloxacin (+) water (-) Staphylococcus Aureus ATCC-25925 5mg/ml ---- ---- 5mg/ml ---- ---- ---- ---- 0.625g/ml na Vibrio fluvialis AL004 5mg/ml ---- 5mg/ml 5mg/ml 5mg/ml ---- 5mg/ml 5mg/ml 2.5g/ml na Bacillus cereus ATCC 10702 5mg/ml ---- ---- ---- ---- ---- 5mg/ml ---- 0.313g/ml na Escherichia coli ATCC 10819 5mg/ml ---- ---- ---- ---- ---- 5mg/ml ---- 0.625g/ml na
  24. 24. MINIMUM BACTERICIDAL CONCENTRATION (MBC) Table 2: MBC results for the novel alpha-Hydroxyphosphonates Microorganisms Compounds Control(+) C1 C3 C4 C5 C7 C8 Ciprofloxacin Staphylococcus aureus ATCC-25925 > 5mg/ml 5mg/ml >5mg/ml >5mg/ml >5mg/ml >5mg/ml >5g/ml Vibrio fluvialis AL004 > 5mg/ml >5mg/ml >5mg/ml >5mg/ml >5mg/ml >5mg/ml >5g/ml Bacillus cereus ATCC 10702 > 5mg/ml >5mg/ml >5mg/ml >5mg/ml >5mg/ml >5mg/ml >5g/ml Escherichia coli ATCC 10819 >5mg/ml >5mg/ml >5mg/ml >5mg/ml >5mg/ml >5mg/ml 5g/ml
  25. 25. ANTICANCER ACTIVITY The discovery of lung cancer and other cancers can synthesize and secrete acetylcholine by these cancers (Song and Spindel, 2008). The inhibition of the enzyme Acetylcholinesterase can decrease the risk of the development of cancer. The anticancer activity was determined using the Acetylcholinesterase Assay Kit (MAK119). AChEActivity(units/L)=(A412)final(A412)initial x200 (A412)calibrator(A412)blank
  26. 26. ACETYLCHOLINESTERASE ACTIVITY Table 1: The results showing the activity of Acetylcholinesterase at 1mg/ml of the compound (in 100 % DMSO). Compound Acetylcholinesterase activity 1 -33.63 2 -49.78 3 +14.80 4 +14.57 5 +9.64 6 -19.73 7 -81.84 8 -22.87 KEY: - No activity + Activity
  27. 27. TABLE 2: The results showing the Acetylcholinesterase activity at 0.1mg/ml of the compound ( in 100% methanol). Compound Acetylcholinesterase activity 1 -27.62 2 -27.11 6 74.68 7 -23.02 8 -134.53
  28. 28. CONCLUSION A convenient high-yielding one-pot, two-component reaction of various aldehydes with dialkylphosphite was successfully accomplished via Abramov reaction without any by- products. 1,4-Dimethylpiperazine was proved to be an efficient catalyst in all the reactions. The highlighting advantages of Abramov reaction. The results of the antibacterial and anticancer activities revealed that the 8 compounds screened had the bioactivities that were performed.
  29. 29. Further work from this project To perform some more bioactivities such as the anti- fungal and antiviral activities of the newly synthesized compounds.
  30. 30. Acknowledgements I would like to thank the following people: Prof A.R Opoku (supervisor) : Dr C Sampath (Co-Supervisor) : Dr R.A Mosa and Dr D Penduka (f (for helping out with bioactivities)
  31. 31. REFERENCES K. B. Dillon, F. Mathey and J. F. Nixon, Phosphorus. The Carbon Copy, John Wiley. & Sons, New York, 1998. Song Pingfang and Eliot R. Spindel (2008), Basic and clinical aspects of non-neuronal Acetylcholine: expression of non-neuronal acetylcholine lung cancer for therapy, Journal of pharmalogical sciences, (106): 180-185. Todd, Science, 127,787, 1958. Reddy S. Subba, Ch. SyamaSundar, S. Siva Prasad, E. Dadapeer, C. Naga Raju and C. Suresh Reddy. (2012), Synthesis, spectral characterization and antimicrobial activity of -hydroxyphosphonates, Der Pharma Chemica, 4(6):2208-2213. O. M. Friedman, E. Boger, V. Grubliauskas and H. Sommer, J. Med. Chem., 6, 50, 1963. A. N. Pudovik, I. V. Konovalova, Synthesis, 81, 1979.

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