Synthesis of Certain Novel Heterocyclic Compounds and their Possible Biological Activities

Abstract

After analysing the results of the present work, the following conclusions were made. From millions of hits existing in various databases, virtual screening technique has helped in filtering the unwanted hits and thus focussing only on the leads that were having an affinity towards the aimed enoyl ACP reductase enzyme. Insilico lead optimisation has helped in further filtering of the leads by avoiding pharmacokinetically inferior compounds from two hundred derivatives optimized, thus authenticating the drug like nature of the forty five leads selected for further studies. The docking study performed has confirmed the affinity of the selected leads towards the enzyme, enoyl ACP reductase from Mycobacterium tuberculosis and Escherichia coli. The antitubercular activity data revealed that the compounds with both the diphenyl ether and pyrrolidine carboxamide scaffolds were possessing significant activity. Also thiadiazole and oxadiazine incorporated derivatives in both the series were found to be the most active. The antibacterial screening reports suggested that among the novel diphenyl ether analogs and pyrrolidine carboxamides synthesized, diphenyl ether scaffold was found to be more significant. Since diphenyl ether based biocide agent triclosan and pyrrolidine carboxamides are reported as having the antitubercular and antibacterial activity attributed to the enoyl ACP reductase enzyme inhibition, the novel drugs designed and synthesized with these basic scaffolds in the present study, can be substantiated as possessing the corresponding activity due to the enoyl ACP reductase enzyme inhibition. Therefore these novel agents can be significant as direct enoyl ACP reductase and can be further evaluated for their enzyme inhibitory assay as a future perspective. The present work has resulted in the utilization of novel computational drug design technique in the investigation and design of potential drugs of medicinal interest. newline