Cytotoxic Activity of Flavone Analogues

Afroze Alam, U Farooq, Kamlesh Kumar Naik, Rashmi Singh, Vachaspati Dubey, Monika Verma, B D Tripathi, Vinod Kumar


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, and 26.35 μg/ml respectively, in comparison
to standard molecule Cisplastin had IC50 value 6- 12.5 μg/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.


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

Full Text:



Foye WO. Principle of Medicinal chemistry. 3rd Ed.

Verghese Publishing house, Bombay; 1989 .

Karle BK , Hangargo RV ,Mane AS, Gill CH , Shingare

MS. Ind. J. Hetrocyclic chem. 2001; 11: 81-82.

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.

Finar IL. Organic Chemistry volume 2. 5th ED. Pearson

Education Asia Ltd.

Ahluwalia VK, Parashar RK. Organic reaction mechanism

and applications. 1st Ed .Narosa Publishing House.

Lynda LS , Jerome KW , Sang K, Lee CG , Dial L ,

Richard CM , Robert MM ,John MP . Cancer Research.

Feb ;59.

Silvia G, Cavalli A. Cytochrome P450 aromatase

inhibitors. J.Med. Chem2006;49:4777- 4780.

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

Havsteen BH ( 2002). The biochemistry and medical

significance of the flavonoids. Pharmacol. Therap.96.

P. 67-202.

Richardson MA (2001). Biopharmacologic and herbal

therapies for cancer: research update from NCCAM.

J. Nut. 131:3037S–3040S.

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.

Block, J. H.; Beale, J. M. Jr. Wilson and Gisvold’s Textbook

of Organic, Medicinal and Pharmaceutical Chemistry.


edition, Lippincott. Williams and Wilkins. 2004,


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,.

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,


Selassie, C. D. History of Quantitative Structure-Activity

Relationship. Burger’s Medicinal Chemistry and Drug

Discovery. Vol I. 6


edition. Wiley Intersciences 2003,


Taylor, P. J. Hydrophobic Properties of Drug.

Comprehensive Medicinal Chemistry Vol IV. 1



edition. Pergamon Press Elsevier, 2005, 270-273 .

Beckett, A. H.; Stenlake, J. B. Practical Pharmaceutical

Chemistry. 4


edition part-II. CBS Publishers and

Distributors. 2005, 275-278.

Markandi JK , Shashi , Surender k. Ind .J. Chem. 2004

April 43B :895-896.

Wattenberg LW. Inhibition of carcinogenesis by

minor dietary constituents. Cancer Res 1992 ;52:


Calomme M, Pieters L, Vlietinck A, Vanden Berghe D.

Inhibition of bacterial mutagenesis by Citrus flavonoids.

Planta Med 1996; 62: 222–226.

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.

Williamson G, Faulkner K, PlumbGW. Glucosinolates

and phenolic as antioxidants from plant foods. Eur J

Cancer Prev 1998;7:17–21.

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.

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.

Tsyrlov IB, Mikhailenko VM, Gelboin HV. Isozyme- and

species-specific susceptibility of cDNA expressed CYP1A

P-450s to different flavonoids. Biochim Biophys Acta

; 1205: 325–335.

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.

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


Brueggemeier RW. Aromatase, inhibitors, and breast

cancer. Am J Ther 2001;8: 333–344.

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:


Jeong HJ, Shin YG, Kim IH, Pezzuto JM. Inhibition of

aromatase activity by flavonoids. Arch Pharm Res1999;

: 309–312.

Wang C, Makela T, Hase T, Adlercreutz H, Kurzer MS.

Lignans and flavonoids inhibit aromatase enzyme in

human preadipocytes. J Steroid Biochem Mol Biol

;50: 205–212.

Birt DF, Hendrich S, Wang W. Dietary agents in cancer

prevention: Flavonoids and Isoflavonoids. Pharmacol

Ther 2001;90: 157–177.

Wang HK. The therapeutic potential of flavonoids.

Expert Opin Invest Drugs 2000;9:2103–2119.

Le Marchand L. Cancer preventive effects of

flavonoids—A review. Biomed Pharmacotherapeutics


Viljanen Johan, Tegler Lotta Broo, IFM, Department of

Organic Chemistry, Linkoeping University Linkoeping,

Swed. Bioconjugate Chemistry. American Chemical

Society. 2004;15(4): 718-727.

Park J, Giew A. Computer-Aided Molecular Design

Laboratory, Mayo Clinic College of Medicine, Rochester,

MN, USA. Journal of Combinatorial Chemistry ,2004;



  • There are currently no refbacks.

Copyright (c) 2018 Journal of Drug Discovery and Development

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.