Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
J Enzyme Inhib Med Chem. 2022 Dec;37(1):686-700. doi: 10.1080/14756366.2022.2036985.
Inhibiting Cyclin-dependent kinase 2 (CDK2) has been established as a therapeutic strategy for the treatment of many cancers. Accordingly, this study aimed at developing a new set of quinazolinone-based derivatives as CDK2 inhibitors. The new compounds were evaluated for their anticancer activity against sixty tumour cell lines. Compounds and showed excellent growth inhibition against the melanoma cell line MDA-MB-435 with GI% of 94.53 and 94.15, respectively. Cell cycle analysis showed that compound led to cell cycle cessation at S phase and G2/M phase revealing that CDK2 could be the plausible biological target. Thus, the most cytotoxic candidates and were evaluated for their CDK2 inhibitory activity and were able to display significant inhibitory action. The molecular docking study confirmed the obtained results. ADME study predicted that had appropriate drug-likeness properties. These findings highlight a rationale for further development and optimisation of novel CDK2 inhibitors.
抑制细胞周期蛋白依赖性激酶 2（CDK2）已被确立为治疗多种癌症的一种治疗策略。因此，本研究旨在开发一系列新的基于喹唑啉酮的衍生物作为 CDK2 抑制剂。这些新化合物的抗癌活性针对六十种肿瘤细胞系进行了评估。化合物 和 对黑色素瘤细胞系 MDA-MB-435 的生长抑制作用非常显著，GI%分别为 94.53%和 94.15%。细胞周期分析表明，化合物 导致 S 期和 G2/M 期的细胞周期停滞，表明 CDK2 可能是合理的生物学靶标。因此，对最具细胞毒性的候选化合物 和 进行了 CDK2 抑制活性评估，结果表明它们具有显著的抑制作用。分子对接研究证实了所得到的结果。ADME 研究预测 具有适当的类药性。这些发现为进一步开发和优化新型 CDK2 抑制剂提供了依据。
