Synthesis and evaluation of benzimidazole carbamates bearing indole moieties for antiproliferative and antitubulin activities.

Abstract

A series of novel benzimidazole carbamates bearing indole moieties with sulphur or selenium atoms connecting the aromatic rings were synthesised and evaluated for their antiproliferative activities against three human cancer cell lines (SGC-7901, A-549 and HT-1080) using an MTT assay. Compounds 10a, 10b, 7a, 7b and 7f showed significant activities against these cell lines. The most potent compound in this series, 10a, was selected to investigate its antitumour mechanism. In addition, molecular docking studies suggested that compound 10a interacts very closely with the nocodazole docking pose through hydrogen bonds at the colchicine binding site of tubulin.

• Authors: Qi Guan, Chunming Han, Daiying Zuo, Min'an Zhai, Zengqiang Li, Qian Zhang, Yanpeng Zhai, Xuewei Jiang, Kai Bao, Yingliang Wu, Weige Zhang
• Journal: European journal of medicinal chemistry (Eur J Med Chem) Vol. 87 Pg. 306-15 (Nov 24 2014) ISSN: 1768-3254 [Electronic] France
• PMID: 25262051 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Chemical References

• Antineoplastic Agents
• Benzimidazoles
• Carbamates
• Tubulin
• Tubulin Modulators
• benzimidazole

Topics

• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Benzimidazoles (chemistry)
• Carbamates (chemical synthesis, chemistry, pharmacology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Chemistry Techniques, Synthetic
• Humans
• Models, Molecular
• Protein Multimerization (drug effects)
• Protein Structure, Quaternary
• Tubulin (chemistry)
• Tubulin Modulators (chemical synthesis, chemistry, pharmacology)