Design and synthesis of new 4-methylthiazole derivatives: In vitro and in silico studies of antimicrobial activity

ABSTRACT The development of resistance against antimicrobial drugs has become a world-wide issue. It is predicted that some or perhaps all the antimicrobial drugs used in clinics will be out of the treatment protocols soon. Therefore, researchers pay more attention to the development of new antimicrobial drugs. For this purpose, we designed and synthesized new 4-methylthiazole-(benz)azole derivatives. The structural elucidation of the compounds was performed by 1H-NMR, 13C-NMR, HSQC, NOESY, HMBC and LC/MS-IT-TOF spectral and elemental analyses. Then, their antimicrobial activity against bacteria and fungi strains was tested. The antibacterial effect of the compounds was found valuable as compared with their anticandidal activity. By combining the findings with molecular docking results, structure-activity relationship (SAR) was explained. Thus, in the development of new antimicrobial agents which can be used as DNA gyrase inhibitors, SAR showed that the products might be used in the discovery of new antimicrobials where their activity is owed to the allosteric effect. Although the effect of compound 3f was modest compared to the reference compound, it was better than the other synthesized compounds. Also, compound 3f has a better allosteric effect and might be a good lead candidate to synthesize new and better active hits. In addition, it was observed that all the synthesized compounds showed half potency against P. aeruginosa compared to the reference drug. On the other hand, no significant difference was seen between compounds against gram-positive or gram-negative bacteria. Briefly, meaningful data to correlate the SAR with thiazole-(benz)azole hybridized compounds were presented in this study. In future projects, the mentioned ideas can be used to synthesize new compounds having better antibacterial activity, particularly against resistant organisms.