Chin. J. Org. Chem. ›› 2018, Vol. 38 ›› Issue (11): 3039-3047.DOI: 10.6023/cjoc201805035 Previous Articles     Next Articles

Special Issue: 有机小分子-金属协同催化



关梦佳, 邱进, 鲁春华, 赵保兵, 沈月毛   

  1. 山东大学药学院 天然产物化学生物学教育部重点实验室 济南 250012
  • 收稿日期:2018-05-16 修回日期:2018-06-14 发布日期:2018-07-16
  • 通讯作者: 赵保兵
  • 基金资助:


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

Guan Mengjia, Qiu Jin, Lu Chunhua, Zhao Baobing, Shen Yuemao   

  1. Key Laboratory of Chemical Biology(Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan 250012
  • Received:2018-05-16 Revised:2018-06-14 Published:2018-07-16
  • Supported by:

    Project supported by the National Basic Research Program (973 Program, No. 2010CB833802), the National Natural Science Foundation of China (Nos. 81373304, 81273384), the program for Innovative Research Team in University of Ministry of Education of China (No. IRT_17R68) and the National Science Found for Distinguished Young Scholars of China (No. 30325044).

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) μmol/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 Ⅱα (TOP2α), 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 TOP2α, which provide insight into the development of novel terphenyl topoisomerase Ⅱα inhibitors.

Key words: topoisomerase, terphenyls, inhibitor, antitumor