Title:Tubulin Inhibitors Binding to Colchicine-Site: A Review from 2015 to 2019
Volume: 27
Issue: 40
Author(s): Lin-Ying Xia, Ya-Liang Zhang, Rong Yang, Zhong-Chang Wang, Ya-Dong Lu*, Bao-Zhong Wang*Hai-Liang Zhu*
Affiliation:
- Neonatal Medical Center, Children’s Hospital of Nanjing Medical University, Nanjing 210008,China
- Zhengzhou Children’s Hospital, Zhengzhou 450018,China
- Zhengzhou Children’s Hospital, Zhengzhou 450018,China
Keywords:
Tubulin inhibitors, colchicine-site, antitumor activity, multi-drug-resistance, multi-target, domains.
Abstract: Due to the three domains of the colchicine-site which is conducive to the combination
with small molecule compounds, colchicine-site on the tubulin has become a common target for
antitumor drug development, and accordingly, a large number of tubulin inhibitors binding to the
colchicine-site have been reported and evaluated over the past years. In this study, tubulin inhibitors
targeting the colchicine-site and their application as antitumor agents were reviewed based on the
literature from 2015 to 2019. Tubulin inhibitors were classified into ten categories according to the
structural features, including colchicine derivatives, CA-4 analogs, chalcone analogs, coumarin analogs,
indole hybrids, quinoline and quinazoline analogs, lignan and podophyllotoxin derivatives,
phenothiazine analogs, N-heterocycle hybrids and others. Most of them displayed potent antitumor
activity, including antiproliferative effects against Multi-Drug-Resistant (MDR) cell lines and antivascular
properties, both in vitro and in vivo. In this review, the design, synthesis and the analysis of
the structure-activity relationship of tubulin inhibitors targeting the colchicine-site were described in
detail. In addition, multi-target inhibitors, anti-MDR compounds, and inhibitors bearing antitumor
activity in vivo are further listed in tables to present a clear picture of potent tubulin inhibitors, which
could be beneficial for medicinal chemistry researchers.
