Chinese Journal of Organic Chemistry >
Design and Synthesis of Natural Product-Like Terphenyl as Potent Topoisomerase IIα Inhibitors
Received date: 2018-05-16
Revised date: 2018-06-14
Online 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
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
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