Design, Synthesis and Anti-Cancer Evaluation of Imidazopyridine -Thiazole Hybrids.

Abstract

Hybrid heterocyclic frameworks are valuable in anticancer drug discovery as they integrate multiple pharmacophores to enhance biological activity and target specificity. The fusion of imidazopyridine and thiazole moieties can generate novel hybrids with improved cytotoxic potential against breast cancer cells. Objective: This study was designed to rationally develop a series of imidazopyridine–thiazole hybrid conjugates (4a–4g) for their anticancer activity on MCF-7 human breast cancer cells, along with molecular docking analysis to investigate their binding interactions with the target protein. Methods:
A series of imidazopyridine–thiazole derivatives (4a–4g) were synthesized through a multistep process and characterized using spectroscopic techniques. Their cytotoxic activity against MCF-7 cells was evaluated by MTT assay (IC₅₀ determination), along with molecular docking to assess binding affinity and interactions with the target protein. Results and Discussion: The synthesized hybrids exhibited notable cytotoxic activity on MCF-7 cells, with compound 4e showing the highest potency (IC₅₀ = 21.25 μg/mL), followed by 4g (32.29 μg/mL). Molecular docking indicated that compound 4f had the strongest binding affinity (–10.24 kcal/mol) with stable interactions at the active site, suggesting a positive correlation between the imidazopyridine–thiazole hybrid scaffold and enhanced anticancer activity. Conclusion: The synthesized imidazopyridine–thiazole hybrids exhibited promising anticancer activity against MCF-7 breast cancer cells, with compound 4e showing the highest cytotoxic potency (IC₅₀ = 21.25 μg/mL) and compound 4f demonstrating the best binding affinity (–10.24 kcal/mol) in molecular docking studies. Overall, these findings indicate that the imidazopyridine–thiazole scaffold is a potential lead for further optimization in the development of novel anti-breast cancer agents.