Synthesis and biological evaluation of novel carbazole-rhodanine conjugates as topoisomerase II inhibitors

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:28

Article

Jiang, Hong¹  Zhang, Wen-Jin¹  Li, Peng-Hui¹  Wang, Jian²  Dong, Chang-Zhi^1,3  Zhang, Kun^1,4  Chen, Hui-Xiong^1,5  Du, Zhi-Yun¹ 

[1] Guandong Univ Technol, Sch Chem Engn & Light Ind, Inst Nat Med & Green Chem, Guangzhou 510006, Guangdong, Peoples R China

[2] Tsinghua Univ, Sch Pharmaceut Sci, Beijing 100084, Peoples R China

[3] Univ Paris Diderot, Sorbonne Paris Cite, CNRS, ITODYS,UMR 7086, 15 Rue J-A Baif, F-75270 Pairs 13, France

[4] Wuyi Univ, Jiangmen 529020, Peoples R China

[5] Univ Paris 05, Sorbonne Paris Cite, CNRS,UMR8601,CBNIT,PRES, Lab Chim & Biochim Pharmacol & Toxicol,UFR Bio5me, 45 Rue St Peres, F-75270 Paris 06, France

关键词: Carbazole;    Rhodanine;    Topoisomerase II;    Cytotoxic;    Hybrid molecule;   

DOI  :  10.1016/j.bmcl.2018.03.017

来源: Elsevier

【 摘 要 】

In this study, a series of carbazole-rhodanine conjugates was synthesized and evaluated for their Topoisomerase II inhibition potency as well as cytotoxicity against a panel of four human cancer cell lines. Among these thirteen compounds, 3a, 3b, 3g, and 3h possessed Topoisomerase II inhibition potency at 20 mu M. Mechanism study revealed that these compounds may function as Topo II catalytic inhibitors. It was found that the electron-withdrawing groups on the phenyl ring of compounds played an important role on enhancing both enzyme inhibition and cytotoxicity. (C) 2018 Elsevier Ltd. All rights reserved.

【 授权许可】

Free