Tailor made biheterocyclic pyrazoline-thiazolidinones as effective inhibitors of Escherichia coli FabH: Design, synthesis and structural studies

In the present study, a new series of biheterocycles pyrazoline-thiazolidinones derivatized at fifth position with substituted arylidene groups were developed as potent inhibitors of Escherichia coli FabH (PDB: 5BNS) an antimicrobial target. These compounds are conveniently synthesized from 3,5-substituted pyrazolinyl carbothioamide precursor. The virtual inhibition assay and pharmacokinetic profiling were carried out based on in vitro antimicrobial assay on pathogenic microbes. Amongst, the compound with 4-methoxy benzylidene substituent emerged as effective against all tested bacterial strains. The compound binds very effectively to the active site of the target with minimum glide score = −8.400 kcal/mol. The structure of newly synthesized derivatives was confirmed by several spectroscopic techniques and some of the hybrids by single crystal XRD studies. The compounds 3, 4a and 4g were crystallized in monoclinic crystal system with P21/c, P21/n and Cc space group respectively. The intermolecular contacts in the crystal structure were elucidated by Hirshfeld computational methods and molecular electrostatic potential maps illustrated the charge distribution of the molecules.