Synthesis and Pharmacological Evaluation of Piperazine Substituted Dehydroacetic Acid (Pyrone) Derivatives

Abstract

Various chalcone derivatives (MDA1 to MDA8) were synthesized from the intermediate, 3-acetyl-6-methyl-4-[4-(4-methylpiperazin1-yl)butoxy)]-2H-pyran-2- one using different aromatic aldehydes by Claisen Schmidt condensation reaction at 0-5°C. This intermediate was obtained from 3-acetyl-4-hydroxy-6-methyl-3,4- dihydro-2H-pyran-2-one by treatment with 1,4-dibromobutane in presence of basic catalyst followed by heating with N-methylpiperazine. The synthesized compounds were confirmed by IR, 1H NMR and Mass spectral data. All title compounds were investigated for the in-vivo anticancer activity by using Ehrlich ascites carcinoma cells and in-vitro antimicrobial activity against Gram negative and Gram positive bacteria. Compounds MDA4, MDA5, MDA6 and MDA7 with electron releasing groups like –OCH3 and –N(CH3)2 in phenyl ring, were found to have extremely significant anticancer activity and more percentage increase in life span and mean survival time which was comparable to standard 5-flurouracil. These compounds have also shown significant broad spectrum antibacterial activity against E. coli (MTCC-4351), P. aeruginosa (MTCC 424), B. subtilis (MTCC-441), S. aureus (MTCC 3160). Other synthesised compounds MDA1, MDA2, MDA3 and MDA8 with electron withdrowing groups like –Cl, -NO2 etc were found to be inactive as anticancer as well as antibacterial.