Design, Synthesis, Anticancer Activity and Docking Studies of Thiazole Linked Phenylsulfone Moiety as Cyclin-Dependent Kinase 2 (CDK2) Inhibitors

Inhibition of the cyclin dependent kinase 2 (CDK2) is a well-known cancer treatment approach. Based on molecular docking simulation analysis, two new series 2-(1-(4-methoxyphenyl)-2-(phenylsulfonyl)ethylidene)hydrazineylidene)-2,5-dihydrothiazole as CDK-2 inhibitors were designed. The lead compound IV (5-benzoyl-N2-phenyl-1,3-thiazole-2,4-diamine) was modified and optimized prior to this analysis. In contrast Roniciclib (−8.6 kcal/mol), results CDK2 hits showed high affinity scores ranging from −9.1 −10.3 kcal/mol. All compounds studied evaluated in vitro for inhibitory activity. comparison Roscovitine's IC50 0.432 µM, 11b had maximum 0.416 µM. Additionally, all tested antiproliferative activities against PC-3 human prostate cells, HEPG-2 hepatocellular carcinoma, MCF-7 breast adenocarcinoma cell lines. arylhydrazine moiety 11a–e demonstrated potency HEPG-2, with (IC50 = 0.11 µM) being more active than doxorubicin 0.12 µM). addition, 0.245 nearly effective 0.246 cells. 11d superior activity line (IC50= 0.23 relative 0.29