Insights into antimicrobial potential of functionalized thiazoles: In vitro and in silico analysis

Abstract

Thiazole heterocycles hold significance in drug design and discovery. Thiazoles constitute effective antimicrobial drugs like Cephalosporins (Antibacterial) and Thiabendazole (Antifungal). The presence of sulfur and nitrogen atoms turn thiazole significant motif for co-ordination purposes improving therapeutic efficacy. Similarly, substitution of thiazole ring generates biosafe analogues with desired pharmacokinetic profile. Therefore, thiazole motif serves as versatile tool for hit to lead generation and subsequent optimization. In this context, the current review (2021–2023) contains synthesis, in vitro antimicrobial screening and molecular docking analysis of thiazole based heterocycles. The core objectives include: (i) To discuss thiazole based available drugs and therapeutic candidates under clinical trails; (ii) Efficient strategies for the synthesis of thiazole heterocycles; (iii) Recent advances in antibacterial and antifungal potential of thiazole derivatives; (iv) Structure activity relationships (SARs) of antimicrobial thiazole analogues; (v) Molecular docking (MD) analysis of the potent antimicrobials to gain insight into the intermolecular interactions present between thiazole and the target protein. Briefly, the efficient synthetic strategies include condensation reactions, multicomponent reactions, microwave irradiation, nanocatalysis, cycloaddition reactions and hemi synthesis. Consequently, the screened thiazole derivatives showed potency against various bacterial and fungal strains with some of the hybrids having better inhibition against the resistant strains than the standard drugs. Thiazole hybrids exhibited higher antimicrobial potential than simple thiazoles and their co-ordination compounds. SARs analysed the antimcrobial effects of various electron donating groups (EDGs) and electron withdrawing groups (EWGs) around thiazole ring. MD analysis revealed significant interactions of the screened thiazole derivatives with the target proteins augmenting their higher inhibition. Thus, this review encourages researchers to explore thiazole heterocycle further by designing novel thiazole derivatives through in silico analysis, perform their optimum synthesis and evaluate in in vitro antimicrobial assay against resistant microbial strains for potent derivatives.