Synthesis and Biological Evaluation of 3-Aryl Pyrazoles as CDK2/HDAC Inhibitor for Anticancer Agents

摘要

A novel series of pyrazole derivatives containing hydroxamic acid group were designed and synthesized as multi-target inhibitors targeting CDK2 (cyclin-dependent kinases 2) and HDAC (histone deacetylase). Compounds 6e and 6f exhibited most potent CDK2 inhibition as well as HDAC inhibition. In vitro antiproliferative assay indicated that several compounds showed better antiproliferative potency compared to olomoucine and SAHA. Docking simulation suggested a common mode of interaction at the active binding sites of CDK2 and HDAC, which demonstrates that compound 6f is a potential agent for cancer therapy deserving further researching.