Discovery of novel 2-phenyl-imidazo[1,2-a]pyridine analogues targeting tubulin polymerization as antiproliferative agents

Weiteng An; Wei Wang; Ting Yu; Yongliang Zhang; Zehong Miao; Tao Meng; Jingkang Shen

doi:10.1016/j.ejmech.2016.02.004

Discovery of novel 2-phenyl-imidazo[1,2-a]pyridine analogues targeting tubulin polymerization as antiproliferative agents

Eur J Med Chem. 2016 Apr 13:112:367-372. doi: 10.1016/j.ejmech.2016.02.004. Epub 2016 Feb 5.

Authors

Weiteng An¹, Wei Wang¹, Ting Yu¹, Yongliang Zhang¹, Zehong Miao², Tao Meng³, Jingkang Shen⁴

Affiliations

¹ State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, PR China.
² State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, PR China. Electronic address: zhmiao@simm.ac.cn.
³ State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, PR China. Electronic address: tmeng@sibs.ac.cn.
⁴ State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, PR China. Electronic address: jkshen@simm.ac.cn.

PMID: 26927488
DOI: 10.1016/j.ejmech.2016.02.004

Abstract

A series of 2-aryl-imidazo-pyridines/pyrazines derivatives has been designed, synthesized and evaluated for their biological activities. Among them, several investigated compounds (1a, 3b and 3d) displayed potent antiproliferative activity against HeLa cell, and also displayed comparable tubulin polymerization inhibitory activity to colchicine. These studies provided a new molecular scaffold for the further development of antitumor agents that target tubulin.

Keywords: Anticancer agents; Colchicine binding site; Intra-molecular hydrogen bonding; Tubulin inhibitor.

MeSH terms

Antineoplastic Agents / chemistry*
Antineoplastic Agents / pharmacology*
Cell Proliferation / drug effects*
Colchicine / pharmacology
Crystallography, X-Ray
HeLa Cells
Humans
Imidazoles / chemistry
Imidazoles / pharmacology
Models, Molecular
Neoplasms / drug therapy
Neoplasms / metabolism
Pyridines / chemistry*
Pyridines / pharmacology*
Tubulin / metabolism
Tubulin Modulators / chemistry*
Tubulin Modulators / pharmacology*

Substances

Antineoplastic Agents
Imidazoles
Pyridines
Tubulin
Tubulin Modulators
Colchicine