Stereo-Electronic, Molecular Connectivity, and Geometric Configuration Approaches towards Designing Antibacterial Agents from 1, 3, 4-Thiadiazole as the Starting Molecular Template

Abstract

New 5-amino-1,3,4-thiadiazole-2-thiol derivatives have been synthesized based on molecular target designs derived from various molecular descriptors involving configurational geometry, molecular size, and stereoelectronic effects of the desired sub-structural templates using molecular connectivity design approach. The approach generated fragment-based pharmacophore sub-units in comparison to fluoroquinolone template to yield comparable leads with medium molecular size, and nearly flat-plane molecular geometry framework. The product, namely, 5-{[-1-(4-chlorophenyl)-5-phenyl penta-2,4-dien-1-ylidene] amino}-1,3,4-thiadiazole-2-thiol (2 f) showed potent antibacterial activity against both gram-positive and, gram-negative strains to validate the design.