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

Hong Jiang; Wen-Jin Zhang; Peng-Hui Li; Jian Wang; Chang-Zhi Dong; Kun Zhang; Hui-Xiong Chen; Zhi-Yun Du

doi:10.1016/j.bmcl.2018.03.017

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

Bioorg Med Chem Lett. 2018 May 1;28(8):1320-1323. doi: 10.1016/j.bmcl.2018.03.017. Epub 2018 Mar 6.

Authors

Hong Jiang¹, Wen-Jin Zhang¹, Peng-Hui Li², Jian Wang³, Chang-Zhi Dong⁴, Kun Zhang⁵, Hui-Xiong Chen⁶, Zhi-Yun Du⁷

Affiliations

¹ Institute of Natural Medicine & Green Chemistry, School of Chemical Engineering and Light Industry, Guandong University of Technology, Guangzhou 510006, China.
² Institute of Natural Medicine & Green Chemistry, School of Chemical Engineering and Light Industry, Guandong University of Technology, Guangzhou 510006, China. Electronic address: liphsiming@163.com.
³ School of Pharmaceutical Sciences, Tsinghua University, Beijing 100084, China.
⁴ Institute of Natural Medicine & Green Chemistry, School of Chemical Engineering and Light Industry, Guandong University of Technology, Guangzhou 510006, China; Universite Paris Diderot, Sorbonne Paris Cite, ITODYS, UMR 7086 CNRS, 15 rue J-A de Baif, 75270 Cedex 13 Pairs, France.
⁵ Institute of Natural Medicine & Green Chemistry, School of Chemical Engineering and Light Industry, Guandong University of Technology, Guangzhou 510006, China; Wuyi University, Jiangmen 529020, China.
⁶ Institute of Natural Medicine & Green Chemistry, School of Chemical Engineering and Light Industry, Guandong University of Technology, Guangzhou 510006, China; CNRS, UMR8601, Laboratoire de Chimine et Biochimie Pharmacologiques et Toxicologiques, CBNIT, Universite Paris Descartes PRES Sorbonne Paris Cite, UFR Bio5medicale, 45 rue des Saints-Peres, 75270 Paris Cedex 06, France.
⁷ Institute of Natural Medicine & Green Chemistry, School of Chemical Engineering and Light Industry, Guandong University of Technology, Guangzhou 510006, China. Electronic address: zhiyundu@gdut.edu.cn.

PMID: 29545100
DOI: 10.1016/j.bmcl.2018.03.017

Abstract

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 μM. 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.

Keywords: Carbazole; Cytotoxic; Hybrid molecule; Rhodanine; Topoisomerase II.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / pharmacology*
Carbazoles / chemical synthesis
Carbazoles / pharmacology*
Cell Line, Tumor
DNA Topoisomerases, Type II / metabolism*
Drug Screening Assays, Antitumor
Etoposide / pharmacology
Humans
Intercalating Agents / chemical synthesis
Intercalating Agents / pharmacology
Rhodanine / analogs & derivatives*
Rhodanine / chemical synthesis
Rhodanine / pharmacology*
Topoisomerase II Inhibitors / chemical synthesis
Topoisomerase II Inhibitors / pharmacology*

Substances

Antineoplastic Agents
Carbazoles
Intercalating Agents
Topoisomerase II Inhibitors
Etoposide
Rhodanine
DNA Topoisomerases, Type II