Synthesis, Antimicrobial Activities, and Docking Simulations of Novel Hybrid Molecules Based on Bis‐Thiazole Linked to a Pyridine Core

Abstract

ABSTRACT Bacterial infections are increasingly emerging as a major worldwide concern, causing significant illness and mortality, especially in developing countries. Antimicrobial resistance poses a threat to global public health and advancement. The growing incidence of antibiotic‐resistant bacteria emphasizes the need to find new approaches to fight them with different antimicrobial agents, as current treatments are becoming less effective. Heterocycles are vital in contemporary drug discovery and development. Recent progress in synthetic techniques enables the swift creation of many functionalized heterocyclic compounds, broadening the variety of drug‐like materials available for drug discovery. In this context, a series of new bis‐thiazole derivatives incorporating a pyridine core was efficiently synthesized. The compounds were obtained in good yields through the reaction of suitable α‐haloketones or 2‐α‐keto‐hydrazonoyl chlorides with the corresponding bis(hydrazinecarbothioamide) in dioxane under reflux conditions. The structures of the novel compounds were confirmed via elemental analyses and spectral data. The antibacterial effect of the newly synthesized compounds was evaluated against various bacterial strains. Compound 8a exhibited the highest antibacterial activity against Staphylococcus aureus (25.33 mm inhibition zone), while most tested compounds showed negligible antifungal effect. The minimum inhibitory concentrations (MICs) of the tested compounds against the bacterial species ranged from 4 to 28 mg/mL. Compound 13c showed a binding score of ∆ G = −7.4 kcal/mol, forming 12 key interactions in the molecular docking study, indicating a strong affinity with the target protein. Notably, fluconazole demonstrated antifungal activity against Aspergillus niger and Aspergillus terreus .