Suzuki coupling based synthesis and in vitro cytotoxic evaluation of 7-heteroaryl-substituted camptothecin analogs

Bioorg Med Chem Lett. 2014 Mar 15;24(6):1597-9. doi: 10.1016/j.bmcl.2014.01.049.

Lei Wang ¹, Ying Huang ¹, Jie Zhang ², Linjiang Tong ², Yi Chen ³, Wei Lu ¹, Qingqing Huang ⁴

Affiliations

1 Institute of Drug Discovery and Development, Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, East China Normal University, 3663 North Zhongshan Road, Shanghai 200062, PR China.
2 State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, SIBS, Chinese Academy of Sciences, Shanghai 201203, PR China.
3 State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, SIBS, Chinese Academy of Sciences, Shanghai 201203, PR China. Electronic address: ychen@jding.dhs.org.
4 Institute of Drug Discovery and Development, Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, East China Normal University, 3663 North Zhongshan Road, Shanghai 200062, PR China. Electronic address: qqhuang@sat.ecnu.edu.cn.

PMID: 24529870 DOI: 10.1016/j.bmcl.2014.01.049

Abstract

In an effort to discover potent antitumor agents, a series of novel C-7-heteroaryl-substituted camptothecin derivatives were designed and synthesized via microwave-promoted Suzuki coupling reaction. These analogs were then assessed for cytotoxicity against three human tumor cell lines, A549, HCT116, HT-29, and inhibitory effects on Topoisomerase I. All of the new compounds showed potent inhibition of human tumor cell growth, among which compound 10a showed higher cytotoxic activity than that of SN-38. Furthermore, this series of compounds retained or enhanced Topo I inhibition.

Keywords

Antitumor; C-7-heteroaryl-substituted camptothecin; Camptothecin; Suzuki coupling.

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