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Eur J Med Chem. 2014 Nov 24;87:306-15. doi: 10.1016/j.ejmech.2014.09.071. Epub 2014 Sep 28.

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

Author information

1
Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China.
2
Department of Pharmacology, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China.
3
Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China; Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA.
4
Department of Pharmacology, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China. Electronic address: yingliang_1016@163.com.
5
Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China. Electronic address: zhangweige2000@sina.com.

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.

KEYWORDS:

Antiproliferative activity; Benzimidazole carbamates; Docking; Indole; Synthesis; Tubulin

PMID:
25262051
DOI:
10.1016/j.ejmech.2014.09.071
[Indexed for MEDLINE]

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