Synthesis and biological evaluation of benzofuran-based 3,4,5-trimethoxybenzamide derivatives as novel tubulin polymerization inhibitors.

Abstract

A new series of derivatives characterized by the presence of the 3,4,5-trimethoxylbenzamide substituted benzofurans were synthesized and evaluated for antiproliferative activity against four cancer cell lines and one normal human cell line. Among them, derivative 6g with greatest cytotoxicity significantly inhibited the growth of MDA-MB-231, HCT-116, HT-29 and HeLa cell lines with IC50 values of 3.01, 5.20, 9.13, and 11.09 μM, respectively. Importantly, 6g possessed excellent selectivity over non-tumoral cell lines HEK-293 (IC50 > 30 μM). Moreover, mechanistic studies revealed that 6g induced HeLa cells arrested in G2/M phase in a concentration-dependent manner, and inhibited polymerization of tubulin via a consistent way with CA-4. In general, these observations suggest that 6g is a promising anti-cancer lead and is worth further investigation to generate potential antitumor agents.

• Authors: Qiu Li, Xie-Er Jian, Zhi-Ru Chen, Lin Chen, Xian-Sen Huo, Zi-Hua Li, Wen-Wei You, Jin-Jun Rao, Pei-Liang Zhao
• Journal: Bioorganic chemistry (Bioorg Chem) Vol. 102 Pg. 104076 (09 2020) ISSN: 1090-2120 [Electronic] United States
• PMID: 32683180 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 Elsevier Inc. All rights reserved.

Chemical References

• Benzamides
• Tubulin
• Tubulin Modulators
• 3,4,5-trimethoxybenzamide

Topics

• Benzamides (chemical synthesis, pharmacology, therapeutic use)
• Drug Design
• HeLa Cells
• Humans
• Molecular Structure
• Polymerization (drug effects)
• Structure-Activity Relationship
• Tubulin (chemistry)
• Tubulin Modulators (pharmacology, therapeutic use)