Synthesis, Molecular Docking and Antimicrobial Activity of alpha, beta-Unsaturated Ketone Exchange Moiety for Chalcone and Pyrazoline Derivatives

摘要

Bacterial diseases cause hazardous infections due to the occurrence of bacterial resistance. Drugs production to cure bacterial resistance from natural sources has become ineffective to execute the resisted bacteria due to the unsuitable binding interaction of active sites with the receptors. Drug link to natural products moieties such as chalcones and pyrazolines, which originated from plants extracts, has become attractive among researchers due to its significant pharmaceutical moiety. In this study a series of chalcone derivatives(1 a-d)has been synthesizedviaClaisen-Schmidt condensation, followed by cyclization to form pyrazolines(2 a-d, 3 a-d). Fischer esterification of pyrazolines formed4 a-din moderate to good yield (42.91-88.23 %). Antimicrobial activities of all the synthesized compounds were evaluated againstEscherichia coliandStaphylococcus aureus viadisc diffusion. Among all compounds, pyrazolines3 cand3 dshowed the highest zone of inhibition (17 mm) compared to1 a-d(5-11 mm) and standard ampicillin (11 mm). The exchange of alpha, beta-unsaturated carbonyl showed phenomenal increment in the biological activities. Structure activity relationship of1 a,1 d,3 aand3 dwas analyzedviamolecular docking ofN-terminal domain having deoxyribonucleic acid (DNA) binding protein (4pql) with excellent binding energy of -6.2, -6.6, -7.1 and -7.2 kcal/mol, respectively. This work is significant in designing new drugs with keto-exchange relationship for medicinal industry.