Design, Synthesis, and Antimicrobial Evaluation of Novel 3-(Piperazine-1-yl)-1,2-Benzothiazole-Linked 1,3,4-Oxadiazoles and 1,2,4-Triazoles: Molecular Docking and Structure-Activity Relationship

Novel antibacterial and antifungal agents were synthesized using thiosemicarbazones derived from 3-(piperazin-1-yl) benzo[d]isothiazole as key intermediates. These intermediates facilitated the Synthesis of 3-(piperazin-1-yl) benzo[d]isothiazole-linked 1,3,4-oxadiazoles and 1,2,4-triazoles. The resulting compounds underwent thorough structural characterization via mass spectrometry, H-1 NMR, C-1(3) NMR, and IR spectroscopy. Biological assessments showed that some compounds exhibited moderate to good antimicrobial activity, indicating their potential as promising candidates for further drug development.'' Furthermore, a molecular docking study against DNA gyrase could rationalize the promising antimicrobial activities demonstrated by these molecules. Compounds 10c, 10e, 10h, 11a, 11g, and 11h (MIC 62.5 mg /mL) exhibit good activity, one of the most active analog 10c (Glide score: -9.872, Glide energy: -57.054 kcal/mol) revealed that the major driving force for the binding affinity is a network of favorable van der Waals interactions, and thus, serve as a foundation for structure-based lead optimization.