Computational Design, Metabolism and Toxicity Studies of Some Novel Chalconesemicarbazone Derivatives

Abstract

In the present study we have used pharmacophore hybridization technique of drug design and designed a pharmacophore model 'chalconesemicarbazone', which is having hydrogen acceptor site, hydrogen donor site, lipophilic site etc, which may help in binding with receptors and plays an important role in pharmacological activities. On these observations, we have designed a synthetic scheme to synthesize this pharmacophore and also synthesize some lead compounds. The pharmacophore of the synthesized compound was developed by using ligandscout-2.02 software by minimizing energy with MM3 force field. The possible metabolites and the toxicity of some selected synthesized chalconesemicarbazones were predicted by computational method using Pallas version-3.1 ADME-Tox prediction (metabolism prediction by Mexalert/RetroMex and toxicity prediction by Hazardexpert/ToxAlert) software. Compound 15 has high probability of toxicity. The major pathway of metabolism was found to be p-hydroxylation and amide hydrolysis.