Design, Synthesis, and In-Silico Assessment of Imidazo[2,1-b]thiazol-5-amines for Promising Anti-Bacterial and Anti-Fungal Activity

Introduction: The imidazo[2,1-b]thiazole core structure has gained significant attention due to its biological activity in various bioactive compounds. Its derivatives exhibit antibacterial, anticancer, and anti-inflammatory properties. Based on an extensive literature review, the synthesis of novel imidazo[2,1-b]thiazole derivatives was undertaken to explore their antibacterial potential against resistant bacterial strains. Methods: The synthesis of the imidazo[2,1-b]thiazole derivatives was performed in three steps: Step 1: The reaction of 5-methylthiazol-2-amine with phenacyl bromide led to the formation of 2-methyl-6-phenylimidazo[2,1-b]thiazole. Step 2: This intermediate was then treated with N-bromo-succinimide (NBS) to form 5-bromo-2-methyl-6-phenylimidazo[2,1-b]thiazole. Step 3: The final derivatives, 5-bromo-2-methyl-6-phenylimidazo[2,1-b]thiazol-5-amine, were synthesized by fur-ther functionalization. The compounds were characterized using TLC, FTIR, 1H NMR, and ESI-MS. Their antibacterial activity was evaluated against Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli, Bacillus subtilis, Candida albicans, and Aspergillus niger. Results: The derivatives 6a, 6b, 6i, and 6o exhibited strong antibacterial activity, especially against P. aeruginosa and S. aureus, with zones of inhibition comparable to ciprofloxacin. Compounds 6a, 6b, 6j, 6l, and 6o also showed potent activity against E. coli and B. subtilis. Conversely, compounds 6c, 6e, 6i, 6j, 6l, 6n, along with 6o, showed highly potent antifungal properties against C. albicans and A. niger. Discussion: The synthesized imidazo[2,1-b]thiazole derivatives demonstrated significant antibac-terial and antifungal activity, notably against resistant pathogens, showing promise as alternative therapies. However, the lack of in vivo and mechanistic investigations restricts findings, requiring more study for clinical confirmation. Conclusion: The synthesized imidazo[2,1-b]thiazole derivatives exhibited significant antibacterial properties, making them promising candidates for further development as antibacterial agents.