Zhang Jian, Ji Fu-Jian, Gu Ye, Zhang Xin-Yao, Qiao Shi-Xing
Department of General Surgery, The Second Hospital, Jilin University, Changchun City, PR China.
School of Public Health, Jilin University, Changchun City, PR China.
Pharmacol Rep. 2014 Jun;66(3):515-9. doi: 10.1016/j.pharep.2013.08.016. Epub 2014 Mar 4.
To discover novel cell division cycle 25 (CDC25) B inhibitors and elucidate the mechanisms of inhibition in cancer cells. Nineteen 2'-hydroxy-4'-isoprenyloxychalcone derivatives (a-s) were evaluated the inhibition CDC25B activity. The enzymatic activities of the CDC25B catalytic domain were determined by monitoring the dephosphorylation of OMFP. Cell growth inhibition was detected by MTT assay. The results showed that sixteen compounds significantly inhibited cycle 25B phosphatase in vitro. Among, three compounds k, r and s had the best inhibition activity and significantly inhibited CDC25B with inhibition rates against CDC25B of 99.95%, 99.75%, and 97.77%, respectively, which is similar to the reference drugs Na3VO4 (98%). Cytotoxic activity assays showed compounds k and r are the potent against HCT116, HeLa, and A549 cells, moreover, compound k delayed the potent tumor inhibitory activity in a colo205 xenograft model in vivo.
为发现新型细胞分裂周期25（CDC25）B抑制剂并阐明其在癌细胞中的抑制机制。评估了19种2'-羟基-4'-异戊烯氧基查尔酮衍生物（a-s）对CDC25B活性的抑制作用。通过监测OMFP的去磷酸化来测定CDC25B催化结构域的酶活性。采用MTT法检测细胞生长抑制情况。结果表明，16种化合物在体外显著抑制周期25B磷酸酶。其中，化合物k、r和s具有最佳抑制活性，对CDC25B的抑制率分别为99.95%、99.75%和97.77%，与参考药物Na3VO4（98%）相似。细胞毒性活性测定表明，化合物k和r对HCT116、HeLa和A549细胞具有强效作用，此外，化合物k在体内的colo205异种移植模型中具有延迟的强效肿瘤抑制活性。
