Design, Molecular Docking, Synthesis, Characterization and Biological Activities of Novel Thiazole Derivatives

Aim: The study aims to design and synthesize novel thiazole derivatives as potent antitubercular agents with minimal side effects. Background: The emergence and rapid spread of multi-drug resistant infectious microbial flora embracing a variety of bacterial as well as mycobacterium strains are causing a threat to public health worldwide. Objective: Owing to the importance, we designed compounds with thiazole functionality coupled with Schiff base and thiosemicarbazide, predicted the molecular properties and antitubercular potency of designed compounds by the in-silico method, and synthesized fifteen novel thiazole analogs, characterized and tested in vivo antitubercular, antibacterial and antioxidant potencies. Methods: Molinspiration online tool was used to predict the molecular properties and molecular docking was used to predict the antitubercular potency. FT-IR, ¹H-NMR, ¹³C-NMR, Mass spectroscopy and bases of elemental analysis are employed to confirm the structure of compounds. 10-Fold serial dilution method, agar streak dilution test and DPPH radical scavenging methods are used to estimate antitubercular, antibacterial and antioxidant potency of title analogs, respectively. Results: Multi-step synthesis was used to synthesize a variety of novel thiazole derivatives coupled with Schiff base and thiosemicarbazide. Synthesized title compounds displayed a varying degree of antitubercular, antibacterial and antioxidant activities (mild to good). The title compounds possessing deactivating group exhibited superior activities than activating group, while unsubstituted analogs displayed intermediate activities. In addition, para-substituted analogs showed slightly higher activity than the corresponding meta substituted analogs. Conclusion: Among fifteen tested title compounds, the potent compound of this series was found to be 1- (4-nitrobenzylidene)-4-(4-(4-methoxyphenyl)thiazol-2-yl)thiosemicarbazide (BTS14), which might be extended as a novel class of antitubercular and antibacterial agents.