Synthesis, Characterization, and Anticancer Studies of Some Pyrazole‐Based Hybrid Heteroatomics

• Published in: ChemistrySelect (Weinheim) 2020-09, Vol.5 (35), p.10827-10834
• Main Authors: Kuthyala, Sharanya, Sheikh, Sareen, Prabhu, Ashwini, Rekha, P. D., Karikannar, Nagaraja G., Shankar, Madan K.
• Format: Article
• Language: English
• Subjects: Cell death analysis; crystal growth; Docking; Drug discovery; MTT Assay
• ISSN: 2365-6549; 2365-6549
• DOI: 10.1002/slct.202002483

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‐1H‐pyrazol‐4‐yl)‐1H‐pyrazol‐4‐yl)pyridine‐3,5‐dicarboxylate (5 b) with spacegroup C2/c. MTT assay provided the anticancer property of the compounds Diethyl1,4‐dihydro‐3,5‐dimethyl‐4‐(3‐(5‐methyl‐1‐phenyl‐1H‐pyrazol‐4‐yl)‐1H‐pyrazol‐4‐yl)pyridine‐2,6‐dicarboxylate (5 a) and 5‐methyl‐1‐phenyl‐4‐(4‐(4,5‐diphenyl‐1H‐imidazol‐2‐yl)‐1H‐pyrazol‐3‐yl)‐1H‐pyrazole (6 a) against A549 cell lines with the IC50 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. Pyrazole based hybrids were successfully synthesized. The X‐Ray crystallography revealed the monoclinic crystal system of Dimethyl 1,4‐dihydro‐2,6‐dimethyl‐4‐(3‐(5‐methyl‐1‐phenyl‐1H‐pyrazol‐4‐yl)‐1H‐pyrazol‐4‐yl)pyridine‐3,5‐dicarboxylate. The anticancer study suggested the highest activity of Diethyl1,4‐dihydro‐3,5‐dimethyl‐4‐(3‐(5‐methyl‐1‐phenyl‐1H‐pyrazol‐4‐yl)‐1H‐pyrazol‐4‐yl)pyridine‐2,6‐dicarboxylate and 5‐methyl‐1‐phenyl‐4‐(4‐(4,5‐diphenyl‐1H‐imidazol‐2‐yl)‐1H‐pyrazol‐3‐yl)‐1H‐pyrazole with IC50 values of 42.79 μM and 55.13 μM respectively against the A549 cell lines. The cell death analysis suggested, both the compounds caused apoptosis in cancer cells, but no changes in the cellular content of normal cells, indicating selectivity. Additionally, molecular docking studies suggested these compounds as remarkable Cyclin‐dependent Kinase‐2 inhibitors.