Amino Acid Conjugates of Aminothiazole and Aminopyridine as Potential Anticancer Agents: Synthesis, Molecular Docking and in vitro Evaluation.

PURPOSE

The development of resistance to available anticancer drugs is increasingly becoming a major challenge and new chemical entities could be unveiled to compensate this therapeutic failure. The current study demonstrated the synthesis of 2-aminothiazole [() and ()] and 2-aminopyridine [() and ()] derivatives that can target multiple cellular networks implicated in cancer development.

METHODS

Biological assays were performed to investigate the antioxidant and anticancer potential of synthesized compounds. Redox imbalance and oxidative stress are hallmarks of cancer, therefore, synthesized compounds were preliminarily screened for their antioxidant activity using DPPH assay, and further five derivatives , , , , and , with significant antioxidant potential, were selected for investigation of in vitro anticancer potential. The cytotoxic activities were evaluated against the parent (A2780) and cisplatin-resistant (A2780CISR) ovarian cancer cell lines. Further, Molecular docking studies of active compounds were performed to determine binding affinities.

RESULTS

Results revealed that , , and displayed promising inhibition in cisplatin-resistant cell lines in comparison to parent cells in terms of both resistance factor (RF) and IC values. Moreover, proved to be most active compound in both parent and resistant cell lines with IC values 15.57 µM and 11.52 µM respectively. Our docking studies demonstrated that compounds , , and exhibited significant binding affinity with multiple protein targets of the signaling cascade.

CONCLUSION

Anticancer activities of compounds , , and in cisplatin-resistant cell lines suggested that these ligands may contribute as lead compounds for the development of new anticancer drugs.