Design and Synthesis of Natural Product-Like Terphenyl as Potent Topoisomerase IIα Inhibitors

作者：Guan, Mengjia; Qiu, Jin; Lu, Chunhua; Zhao, Baobing^*; Shen, Yuemao

来源：Chinese Journal of Organic Chemistry, 2018, 38(11): 3039-3047.

DOI：10.6023/cjoc201805035

• topoisomerase
• terphenyls
• inhibitor
• antitumor

A series of natural product-like terphenyls were synthesized, and their biological activities were evaluated. 4 ''-Amino-[1, 1':4', 1 ''-terphenyl]-3,4-diol (17) has the most potent cytotoxic activity against the MDA-MB-435 cell line, and the IC50 value is (0.20 +/- 1.12) mu mol/L, which is more potent than compounds X1 and X2 obtained in our previous studies. DNA relaxation test showed that compound 17 had a strong inhibitory effect on topoisomerase II alpha (TOP2 alpha), but not on topoisomerase I (TOP1), which was consistent with the docking analysis results. Our studies demonstrate that N contained substitutes on ring C are important for producing terphenyls with more efficacious activity against TOP2 alpha, which provide insight into the development of novel terphenyl topoisomerase II alpha inhibitors.

• 出版日期2018-11-25
• 单位山东大学