In Vitro Antiplasmodial Activity and Cytotoxic Effect of (Z)-2-Benzylidene-4, 6-Dimethoxybenzofuran-3(2H)-One Derivatives
AbstractBackground: Aurones are naturally occurring compounds that belong to flavenoids family and have antiplasmodial effects. This study investigated some new aurones derivatives against chloroquine sensitive Plasmodium falciparum. Here we report the synthesis, in vitro antiplasmodial activity and cytotoxic evaluation of 11 compound from derivatives of (Z)-2- benzylidene-4, 6-dimethoxybenzofuran-3(2H)-one.Methods: The cytotoxic evaluations of active compounds were performed with MTT (3-[4, 5-dimethylthiazol-2-yl]-2, 5 diphenyltetrazolium bromide) assay on human breast cancer cell lines; MCF7 and T47D.Results: From 11 compounds M3, M6 and M7 compounds showed good antiplasmodial effect against chloroquine-sensitive 3D strain of P. falciparum with IC50 (50% inhibitory concentration) values of 7.82, 7.27 and 2.3 µM respectively. No noticeable toxicity was observed with these compounds when tested against tested cell lines. Conclusion: The replacement of the 4 and 5 positions at ring B of aurone derivatives, with propoxy and bromide (Br) respectively was revealed highly advantageous for their antiplasmodial effect.
Harrison TR, Adams RD, Bennett Jr IL, ResnIk WH, Thorn GW, Wintrobe M. Principles of internal medicine. Academic Medicine. 2012. p. 1246.
de Oliveira RB, de Souza-Fagundes EM, Soares RP, Andrade AA, Krettli AU, Zani CL. Synthesis and antimalarial activity of semicarbazone and thiosemicarbazone derivatives. Eur J Med Chem. 2008;43(9):1983-8.
Singh B, Daneshvar C. Human infections and detection of Plasmodium knowlesi. Clin Microbiol Rev. 2013;26(2):165-84.
WHO. World Malaria Report 2012. World Health Organization; 2012; Available from: http://www.who.int/malaria/publications/world_malaria_report_2012/en/.
Alker AP, Lim P, Sem R, Shah NK, Yi P, Bouth DM, et al. Pfmdr1 and in vivo resistance to artesunate-mefloquine in falciparum malaria on the Cambodian-Thai border. Am J Trop Med Hyg. 2007;76(4):641-7.
Mutabingwa TK. Artemisinin-based combina-tion therapies (ACTs): best hope for malaria treatment but inaccessible to the needy! Acta Trop. 2005;95(3):305-15.
Boumendjel A. Aurones: a subclass of flavones with promising biological potential. Curr Med Chem. 2003;10(23):2621-30.
Kayser O, Kiderlen AF, Brun R. In vitro activity of aurones against Plasmodium falciparum strains K1 and NF54. Planta Med. 2001;67(8):718-21.
Souard F, Okombi S, Beney C, Chevalley S, Valentin A, Boumendjel A. 1-Azaaurones derived from the naturally occuring auounes as potential antimalarial drugs. Bioorg Med Chem. 2010;18(15):5724-31.
Carrasco MP, Newton AS, Goncalves L, Gois A, Machado M, Gut J, et al. Probing the aurone scaffold against Plasmodium falciparum: design, synthesis and antimalarial activity. Eur J Med Chem. 2014;80:523-34.
Kayser O, Kiderlen A, Folkens U, Kolodziej H. In vitro leishmanicidal activity of aurones. Planta Med. 1999;65(4):316-9.
Kayser O, Kiderlen A, Croft S. Natural products as antiparasitic drugs. Parasitol Res. 2003;90(2):S55-62.
Ameta K, Rathore NS, Kumar B, Verastegui M, Gilman RH, Verma B. Synthesis and trypanocidal evaluation of some novel 2-(substituted benzylidene)-5, 7-dibromo-6-hydroxy-1-benzofuran-3 (2H)-ones. Int J Org Chem. 2012;2:295-301.
Zhang M, Xu XH, Cui Y, Xie LG, Kong CH. Synthesis and herbicidal potential of substituted aurones. Pest Manag Sci. 2012;68(11):1512-22.
Lawrence NJ, Rennison D, McGown AT, Hadfield JA. The total synthesis of an aurone isolated from Uvaria hamiltonii: aurones and flavones as anticancer agents. Bioorg Med Chem Lett. 2003;13(21):3759-63.
Trager W, Jensen JB. Human malaria parasites in continuous culture. Science. 1976; 193(4254):673-5.
Ramazani A, Sardari S, Zakeri S, Vaziri B. In vitro antiplasmodial and phytochemical study of five Artemisia species from Iran and in vivo activity of two species. Parasitol Res. 2010;107(3):593-9
Ramazani A, Zakeri S, Sardari S, Khodakarim N, Djadidt ND. In vitro and in vivo anti-malarial activity of Boerhavia elegans and Solanum surattense. Malar J. 2010;9:124
Lambros C, Vanderberg JP. Synchronization of Plasmodium falciparum erythrocytic stages in culture. J Parasitol. 1979;65(3):418-20.
Sangian H, Faramarzi H, Yazdinezhad A, Mousavi SJ, Zamani Z, Noubarani M, et al. Antiplasmodial activity of ethanolic extracts of some selected medicinal plants from the northwest of Iran. Parasitol Res. 2013; 112(11):3697-701.
Finney DJ. The adjustment for a natural response rate in probit analysis. Ann Appl Biol. 1949;36(2):187-95.
Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983;65(1-2):55-63.
Rajabi S, Ramazani A, Hamidi M, Naji T. Artemia salina as a model organism in toxicity assessment of nanoparticles. Daru. 2015;23:20.
Kayser O, Kiderlen AF. Leishmanicidal activity of aurones. Tokai J Exp Clin Med. 1998;23(6):423-6.
Sairafianpour M, Kayser O, Christensen J, Asfa M, Witt M, Staerk D, et al. Leishmanicidal and antiplasmodial activity of constituents of Smirnowia Iranica. J Nat Prod. 2002; 65(12):1754-8.
Di Pietro A, Conseil G, Perez-Victoria JM, Dayan G, Baubichon-Cortay H, Trompier D, et al. Modulation by flavonoids of cell multidrug resistance mediated by P-glycoprotein and related ABC transporters. Cell Mol Life Sci. 2002;59(2):307-22.
Sim HM, Lee CY, Ee PL, Go ML. Dimethoxyaurones: Potent inhibitors of ABCG2 (breast cancer resistance protein). Eur J Pharm Sci. 2008;35(4):293-306.