<i>In vivo</i> evaluation of novel synthetic pyrazolones as CDK9 inhibitors with enhanced pharmacokinetic properties
Ebtehal M. Husseiny, Hamada S. Abulkhair, Samiha A. El‐Sebaey, Manal M. Sayed, Kurls E. Anwer
Abstract
Aim: The structural optimization of our recently reported CDK9 inhibitor to furnish novel aminopyrazolones and methylpyrazolones with improved pharmacokinetics.Materials & methods: The synthesis of the targeted compounds was accomplished via conventional, grinding and microwave-assisted processes. The cytotoxicity of them was assayed against three carcinomas.Results: Analogs 2, 4 and 6 showed significant cytotoxicity and selectivity toward all tested cells. They also displayed potent CDK9 inhibition. Compound 6 arrested MCF-7 cycle at G2/M phase by stimulating the apoptotic pathway. The in vivo biodistribution of radiolabeled compound 6 displayed a potent targeting capability of 131I in solid tumors.Conclusion: Entity 6 is a potent CDK9 inhibitor where 131I-compound 6 can be used as a significant radiopharmaceutical imaging tool for tumors.