2. Academic Validation
  3. Synthesis and evaluation of benzimidazole carbamates bearing indole moieties for antiproliferative and antitubulin activities

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

  • Eur J Med Chem. 2014 Nov 24:87:306-15. doi: 10.1016/j.ejmech.2014.09.071.
Qi Guan 1,  Chunming Han 1,  Daiying Zuo 2,  Min'an Zhai 1,  Zengqiang Li 2,  Qian Zhang 1,  Yanpeng Zhai 1,  Xuewei Jiang 2,  Kai Bao 3,  Yingliang Wu 4,  Weige Zhang 5
Affiliations

Affiliations

  • 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.
PMID: 25262051 DOI: 10.1016/j.ejmech.2014.09.071
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.

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