Cytotoxic Activity of Flavone Analogues

Authors

  • Dr. Afroze Alam
  • U Farooq Faculty of Dentistry, Taif University, Taif, Kingdom of Saudi Arabia.
  • Kamlesh Kumar Naik Nandha College of Pharmacy, Perundurai Main Road, Erode, Tamil Nadu-638052, India.
  • Rashmi Singh Narayan Institute of Pharmacy, Jamuhar, Sasaram (ROHTAS) 821305, Bihar, India.
  • Vachaspati Dubey Narayan Institute of Pharmacy, Jamuhar, Sasaram (ROHTAS) 821305, Bihar, India.
  • Monika Verma Department of Paediatrics, Advance Paediatrics Centre, PGIMER, Chandigarh, Punjab-160012.
  • B D Tripathi Narayan Institute of Pharmacy, Jamuhar, Sasaram (ROHTAS) 821305, Bihar, India.
  • Vinod Kumar Narayan Institute of Pharmacy, Jamuhar, Sasaram (ROHTAS) 821305, Bihar, India.

Keywords:

Benzopyrone, Cytotoxic activity, Flavonoids, HeLa cell line, log ‘P’ value, MTT assay

Abstract

The flavonoids are polyphenolic compounds and universally present as constituents of flowering plants,
particularly of food plants. The flavonoids are phenyl substituted chroman (benzopyran derivatives) consisting
of a 15-carbon basic skeleton (C6-C3-C6), composed of a chroman (C6-C3) nucleus (the benzo ring A and
the heterocyclic ring C), also shared by the tocopherols, with a phenyl (the aromatic ring B), substitution
usually at the 2-position. Different substitutions can typically occur in the rings, A and B. Several plants
and spices containing flavonoid derivatives have found application as disease preventive and therapeutic
agents in traditional medicine in Asia for thousands of years. Various analogues of 3-methylflavones
were synthesised, purified and characterised by UV, IR, 1HNMR and mass spectrometry .All the synthesised
compounds were evaluated for their cytotoxic activity by MTT assay against HeLa cell line. Most of the
compounds show moderate activity, whereas the compounds like FA-04.FA-20,FA-10 and FA-13 have
shown good activity having IC50 value 22.00,25.49.26.24 and 26.35 ?g/ml respectively, in comparison
to standard molecule Cisplastin had IC50 value 6- 12.5 ?g/ml . Thus it appears the presence of 3- methyl
group in the flavone nucleus significantly influences the log ‘P’ value of all the twenty test compounds.

The prominent activity the of above compounds is probably because of 3-methyl and N, N-dimethyl amino
substitution on 4’- position of flavonoid nucleus.

References

1. Foye WO. Principle of Medicinal chemistry. 3rd Ed. Verghese Publishing house, Bombay; 1989 .
2. Karle BK , Hangargo RV ,Mane AS, Gill CH , Shingare MS. Ind. J. Hetrocyclic chem. 2001; 11: 81-82.
3. Fritz B ,Tobias S,Albrechts K, Charlotte B ,Kent C , Anni A , Franz J Joseph K . American Soc. Biochem and Mol.
Bio. 1996 Jan ;271(4):2262-2270.
4. Finar IL. Organic Chemistry volume 2. 5th ED. Pearson Education Asia Ltd.
5. Ahluwalia VK, Parashar RK. Organic reaction mechanism and applications. 1st Ed .Narosa Publishing House.
6. Lynda LS , Jerome KW , Sang K, Lee CG , Dial L , Richard CM , Robert MM ,John MP . Cancer Research.
1991 Feb ;59.
7. Silvia G, Cavalli A. Cytochrome P450 aromatase inhibitors. J.Med. Chem2006;49:4777- 4780.
8. Izevbigie EB (2003). Discovery of Water-Soluble Anticancer Agents (Edotides) from a Vegetable Found in
Benin City, Nigeria. Exp. Biol .and Med. 228:293-298.c
9. Havsteen BH ( 2002). The biochemistry and medical significance of the flavonoids. Pharmacol. Therap.96.
P. 67-202.
10. Richardson MA (2001). Biopharmacologic and herbal therapies for cancer: research update from NCCAM.
J. Nut. 131:3037S–3040S.
11. Wolff ME . Burger ‘s Medicinal Chemistry and Drug Discovery 5th Ed . John Wiley and Sons New York.
12. Finar IL. Organic Chemistry volume 2. 5th ED. Pearson Education Asia Ltd.
13. Block, J. H.; Beale, J. M. Jr. Wilson and Gisvold’s Textbook of Organic, Medicinal and Pharmaceutical Chemistry.
11th edition, Lippincott. Williams and Wilkins. 2004, 249,310.
14. Jeffrey M Edmondson, Linda S. Armstrong and Andrew O Martinez. A Rapid and Simple MTT-Based
Spectrophotometric Assay For Determining Drug Sensitivity In Monolayer Culture, Tissue Culture Methods, 1988 11, 15-17,.
15. Rubinstein LV, Shoemaker RH, Paull KD, Sinon RM, Tosini S, Skehan P, Scudiero A Monks, Boyd MR., Comparison of in-vitro Anticancer Drug screening data generated with Tetrazolium Assay Versus a Protein assay Against a Diverse Panel of Human Tumor Cell Lines. Journal of National Cancer Institute, 1990. 82 (13), 1113-1118,
16. http://ecb.jrc.it/DOCUMENTS/Testing-Methods/ANNEXV/AO8web1992.pdf.
17. Selassie, C. D. History of Quantitative Structure-Activity Relationship. Burger’s Medicinal Chemistry and Drug
Discovery. Vol I. 6th edition. Wiley Intersciences 2003, 15-23.
18. Taylor, P. J. Hydrophobic Properties of Drug. Comprehensive Medicinal Chemistry Vol IV. 1st Indian
edition. Pergamon Press Elsevier, 2005, 270-273 .
19. Beckett, A. H.; Stenlake, J. B. Practical Pharmaceutical Chemistry. 4th edition part-II. CBS Publishers and
Distributors. 2005, 275-278.
20. Markandi JK , Shashi , Surender k. Ind .J. Chem. 2004 April 43B :895-896.
21. Wattenberg LW. Inhibition of carcinogenesis by minor dietary constituents. Cancer Res 1992 ;52:
2085s–2091s.
22. Calomme M, Pieters L, Vlietinck A, Vanden Berghe D. Inhibition of bacterial mutagenesis by Citrus flavonoids.
Planta Med 1996; 62: 222–226.
23. Dashwood RH, Xu M, Hernaez JF, Hasaniya N, Youn K, Razzuk A. Cancer chemo preventive Mechanisms of
tea against heterocyclic amine mutagens from cooked meat. Proc Soc Exp Biol Med 1999;220: 239–243.
24. Williamson G, Faulkner K, PlumbGW. Glucosinolates and phenolic as antioxidants from plant foods. Eur J
Cancer Prev 1998;7:17–21.
25. Carroll KK, Guthrie N, So FV, Chambers AF. Anticancer properties of flavonoids, with emphasis on citrus flavonoids. In: Rice-Evans CA, Packer L, editors. Flavonoids in health and disease. New York: MarcelDekker Inc.; 1998. p 437–446.
26. Lahiri-Chatterjee M, Katiyar SK, Mohan RR, Agarwal R. A flavonoid antioxidant, Silymarin, afford exceptionally
high protection against tumor promotion in the SENCAR mouse skin tumorigenesis model. Cancer
Res 1999;59:622–632.
27. Tsyrlov IB, Mikhailenko VM, Gelboin HV. Isozyme- and species-specific susceptibility of cDNA expressed CYP1A
P-450s to different flavonoids. Biochim Biophys Acta 1994; 1205: 325–335.
28. Bu-Abbas A, Clifford MN,Walker R, Ioannides C. Contribution of caffeine and flavanols in the induction
of hepatic Phase II activities by green tea. Food Chem Toxicol 1998; 36: 617–621.
29. Sun XY, Plouzek CA, Henry JP,Wang TT, Phang JM. Increased UDP-glucuronyl transferase activity and
decreased prostate specific antigen production by biochanin A in prostate cancer cells. Cancer
es1998;58:2379–2384.
30. Brueggemeier RW. Aromatase, inhibitors, and breast cancer. Am J Ther 2001;8: 333–344.
31. Pouget C, Fagnere C, Basly JP, Besson AE, Champavier Y, Habrioux G, Chulia AJ. Synthesis and aromatase
inhibitory activity of flavanones. Pharm Res 2002;19: 286–291.
32. Jeong HJ, Shin YG, Kim IH, Pezzuto JM. Inhibition of aromatase activity by flavonoids. Arch Pharm Res1999;
22: 309–312.
33. Wang C, Makela T, Hase T, Adlercreutz H, Kurzer MS. Lignans and flavonoids inhibit aromatase enzyme in
human preadipocytes. J Steroid Biochem Mol Biol 1994;50: 205–212.
34. Birt DF, Hendrich S, Wang W. Dietary agents in cancer prevention: Flavonoids and Isoflavonoids. Pharmacol
Ther 2001;90: 157–177.
35. Wang HK. The therapeutic potential of flavonoids. Expert Opin Invest Drugs 2000;9:2103–2119.
36. Le Marchand L. Cancer preventive effects of flavonoids—A review. Biomed Pharmacotherapeutics
2002;56:296–301.
37. Viljanen Johan, Tegler Lotta Broo, IFM, Department of Organic Chemistry, Linkoeping University Linkoeping,
Swed. Bioconjugate Chemistry. American Chemical Society. 2004;15(4): 718-727.
38. Park J, Giew A. Computer-Aided Molecular Design Laboratory, Mayo Clinic College of Medicine, Rochester, MN, USA. Journal of Combinatorial Chemistry ,2004; 6(3):407-413.

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Published

2018-10-26

How to Cite

Alam, D. A., Farooq, U., Naik, K. K., Singh, R., Dubey, V., Verma, M., Tripathi, B. D., & Kumar, V. (2018). Cytotoxic Activity of Flavone Analogues. Journal of Drug Discovery and Development ( ISSN:2581-6861), 1(1), 13-21. Retrieved from https://medicaljournalshouse.com/index.php/JDrug-Discovery-Development/article/view/49

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Vol. 1 No. 1 (2017): Journal of Drug Discovery and Development

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