Synthesis, Characterization, and Anticancer Studies of Some Pyrazole‐Based Hybrid Heteroatomics
Sharanya Kuthyala, Sareen Sheikh, Ashwini Prabhu, P. D. Rekha, Nagaraja Gundibasappa Karikannar, S. Madan Kumar
Abstract
Abstract Defined with a dual‐mode of action, the hybrid molecule synthesis is an attractive strategy to endure the scientific challenges in drug discovery. Besides worthy development in cancer therapy, it is still a leading cause of death across the globe. Failure in terms of efficacy, selectivity and toxicity, the statistics of a potential drug to concrete the cancer is rather in bleak. In the present study, synthesized hybrid molecules were well characterized by spectroscopy techniques. The single‐crystal X‐ray crystallography study revealed the monoclinic crystal system of Dimethyl 1,4‐dihydro‐2,6‐dimethyl‐4‐(3‐(5‐methyl‐1‐phenyl‐1 H ‐pyrazol‐4‐yl)‐1 H ‐pyrazol‐4‐yl)pyridine‐3,5‐dicarboxylate ( 5 b ) with spacegroup C 2/ c . MTT assay provided the anticancer property of the compounds Diethyl1,4‐dihydro‐3,5‐dimethyl‐4‐(3‐(5‐methyl‐1‐phenyl‐1 H ‐pyrazol‐4‐yl)‐1 H ‐pyrazol‐4‐yl)pyridine‐2,6‐dicarboxylate ( 5 a ) and 5‐methyl‐1‐phenyl‐4‐(4‐(4,5‐diphenyl‐1 H ‐imidazol‐2‐yl)‐1H‐pyrazol‐3‐yl)‐1 H ‐pyrazole ( 6 a ) against A549 cell lines with the IC 50 values of 42.79 μM and 55.13 μM respectively. The AO‐EB staining assay for cell death analysis confirmed the selective action of both 5 a and 6 a . Further, molecular docking confirmed the effective binding with cyclin‐dependent kinase (CDK2) protein, suggesting that the target compounds are remarkable inhibitors in dysregulating the CDK2 protein in cancer cells.