Hydrazineyl-linked imidazole[1,2-a]pyrimidine-thiazole hybrids: design, synthesis, and in vitro biological evaluation studies

Abstract

This research work details the use of a molecular hybridization technique to create a library of four series of hydrazineyl-linked imidazo[1,2-a]pyrimidine-thiazole derivatives. The structure of one of the final products, K2, was validated using single-crystal X-ray diffraction. Twenty-six novel hybrid molecules (K1–K26) were synthesized and tested for activity against the mycobacterium tuberculosis H37Rv strain. Three compounds (K1, K2, and K3) demonstrated significant inhibitory efficacy, with a MIC value of 1.6 μg mL⁻¹. The target compounds also showed significant antibacterial activity against four bacterial strains, namely S. aureus, E. coli, B. subtilis, and P. aeruginosa. In cytotoxicity studies using VERO cells, the potent anti-TB compounds (K1, K2, and K3) showed non-toxic profiles. Furthermore, in silico ADME assessment results, molecular docking (against InhA and CYP121), and DFT studies revealed the active compounds' significant potential as scaffolds for novel antitubercular medicines.