Chen Wang, Shen Yan, Li Zhenyu, Zhang Mengran, Lu Chunhua, Shen Yuemao
Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan, Shandong 250012, PR China.
Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan, Shandong 250012, PR China.
Eur J Med Chem. 2014 Oct 30;86:782-96. doi: 10.1016/j.ejmech.2014.08.073. Epub 2014 Sep 2.
Forty eight 2-phenylnaphthalenoids were designed and successfully synthesized. Their in vitro cytotoxicities against the proliferations of MDA-MB-231, A549 and HeLa cell lines and inhibitory activities on DNA topoisomerase were evaluated. The quantitative structure-activity relationship (QSAR) studies were established on the basis of cytotoxicity data from MDA-MB-231 cell line. Among these compounds, compound 5 showed potent antiproliferative activity (IC50 = 1 μM) against MDA-MB-231 cells and inhibitory activity on topoisomeraseIIα. Further, in vivo antitumor study with xenograft nude mice indicated that compound 5 inhibited the growth of MDA-MB-231 cells and showed lower toxicity than etoposide (VP16). This work indicates that 2-phenylnaphthalenoids represent a novel type of TopoIIα-inhibitory scaffold for developing new antitumor chemotherapeutic agents.
设计并成功合成了48种2-苯基萘类化合物。评估了它们对MDA-MB-231、A549和HeLa细胞系增殖的体外细胞毒性以及对DNA拓扑异构酶的抑制活性。基于MDA-MB-231细胞系的细胞毒性数据建立了定量构效关系（QSAR）研究。在这些化合物中，化合物5对MDA-MB-231细胞显示出强效的抗增殖活性（IC50 = 1 μM）以及对拓扑异构酶IIα的抑制活性。此外，对异种移植裸鼠的体内抗肿瘤研究表明，化合物5抑制了MDA-MB-231细胞的生长，且毒性低于依托泊苷（VP16）。这项工作表明，2-苯基萘类化合物代表了一种新型的拓扑异构酶IIα抑制支架，可用于开发新的抗肿瘤化疗药物。
