title: 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.affiliation: Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Guan
authors.affiliation: Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China.
authors.forename: Chunming
authors.initials: C
authors.lastname: Han
authors.affiliation: Department of Pharmacology, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China.
authors.forename: Daiying
authors.initials: D
authors.lastname: Zuo
authors.affiliation: Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China.
authors.forename: Min'an
authors.initials: M
authors.lastname: Zhai
authors.affiliation: Department of Pharmacology, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China.
authors.forename: Zengqiang
authors.initials: Z
authors.lastname: Li
authors.affiliation: Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China.
authors.forename: Yanpeng
authors.initials: Y
authors.lastname: Zhai
authors.affiliation: Department of Pharmacology, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China.
authors.forename: Xuewei
authors.initials: X
authors.lastname: Jiang
authors.affiliation: 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.
authors.forename: Kai
authors.initials: K
authors.lastname: Bao
authors.affiliation: Department of Pharmacology, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China. Electronic address: yingliang_1016@163.com.
authors.forename: Yingliang
authors.initials: Y
authors.lastname: Wu
authors.affiliation: 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.
authors.forename: Weige
authors.initials: W
authors.lastname: Zhang
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001562:Benzimidazoles / Q000737:chemistry*; D002219:Carbamates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic; D006801:Humans; D008958:Models, Molecular; D055503:Protein Multimerization / Q000187:drug effects; D020836:Protein Structure, Quaternary; D014404:Tubulin / Q000737:chemistry; D050257:Tubulin Modulators / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D001562:Benzimidazoles; D002219:Carbamates; D014404:Tubulin; D050257:Tubulin Modulators; C031000:benzimidazole
keywords: Antiproliferative activity; Benzimidazole carbamates; Docking; Indole; Synthesis; Tubulin