SAR Study of Functionalized Monothiazloe & Bithiazole: A Combined Experimental and Theoretical Approach for Biological Potentials

ABSTRACT In this study, a novel brominated bithiazole compound (8 ) is designed, synthesized, and comprehensively evaluated alongside a previously reported analogue monothiazole (1 ) to check the effect of thiazole rings. The synthetic route involves sequential bromination, condensation, and NBS‐mediated side‐chain bromination, resulting compound (8) with 90% yield, further, confirmed by NMR and HRMS analyses. Density functional theory analysis (B3LYP/6‐311G(d,p)) revealed distinct differences in HOMO–LUMO characteristics, electrostatic potential distribution, and molecular polarity of both the compounds. In vitro anticancer screening against MCF‐7 breast cancer cells revealed that compound (1) exhibited potent cytotoxicity (IC 50 = 1.769 µM), whereas compound (8) showed significantly weaker activity (IC 50 = 269.4 µM). Antimicrobial assays demonstrated broad‐spectrum activity of compound (1) against strain A. niger , B. subtilis , and E. coli , while compound (8) remained largely inactive up to 1000 µmol/disc. SAR study supporting the in vitro results of anticancer and antimicrobial activity. The acetyl group attached with compound (1) is largely responsible for huge disparity in biological results. ADMET predictions further indicates favorable drug‐likeness and safety for compound (1) , whereas compound (8) exhibited solubility and toxicity liabilities. Overall, the study underscores the critical role of structural features in modulating bithiazole bioactivity and identifies compound (1) as a promising lead candidate for further anticancer and antimicrobial development.