Citation: Guan Mengjia, Qiu Jin, Lu Chunhua, Zhao Baobing, Shen Yuemao. Design and Synthesis of Natural Product-Like Terphenyl as Potent Topoisomerase Ⅱα Inhibitors[J]. Chinese Journal of Organic Chemistry, ;2018, 38(11): 3039-3047. doi: 10.6023/cjoc201805035 shu

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

Key Laboratory of Chemical Biology(Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan 250012

Corresponding author: Zhao Baobing, baobingzh@gmail.com
Received Date: 16 May 2018
Revised Date: 14 June 2018
Available Online: 16 November 2018
Fund Project: the National Natural Science Foundation of China 81373304the National Natural Science Foundation of China 81273384the National Basic Research Program 937项目the program for Innovative Research Team in University of Ministry of Education of China IRT_17R68Project 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)the National Science Found for Distinguished Young Scholars of China 30325044the National Basic Research Program 2010CB883802

Figures(5)

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.
- topoisomerase,
- terphenyls,
- inhibitor,
- antitumor
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沈阳化工大学材料科学与工程学院沈阳 110142