Discovery of pyrazole-based analogs as CDK2 inhibitors with apoptotic-inducing activity: design, synthesis and molecular dynamics study.

ABSTRACT: The discovery of novel CDK2 inhibitors is crucial for developing targeted anticancer therapies. Thus, in this study, we aimed to design, synthesize, and evaluate a series of novel pyrazole derivatives (2a-g, 7a-d, 8a and b, 9, and 10) for their potential as CDK2/cyclin A2 enzyme inhibitors. The newly synthesized compounds were screened in vitro at 50 μM for CDK2 inhibition, followed by IC₅₀ profiling of the most promising candidates. Compounds 4, 7a, 7d, and 9 exhibited the strongest inhibition, with IC₅₀ values of 3.82, 2.0, 1.47, and 0.96 μM, respectively. To assess their anti-proliferative effects, all target compounds were further screened against a panel of 60 National Cancer Institute (NCI) cell lines representing various carcinoma types. Among them, comp

SUBMITTER: Ali GME 

PROVIDER: S-EPMC11520566 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature