title: Microwave-assisted synthesis and biological evaluation of 3,4-diaryl maleic anhydride/N-substituted maleimide derivatives as combretastatin A-4 analogues.
abstract: A series of new CA-4 analogues bearing maleic anhydride/N-substituted maleimide moiety were synthesized via a microwave-assisted process. They were evaluated for the anti-proliferative activities against three tumor cell lines (SGC-7901, HT-1080 and KB). Most compounds showed moderate potencies in micromolar range, with the most promising analogue 6f showing active at submicromolar concentration against HT-1080 cancer cells which was selected to investigate the antitumor mechanisms. In addition, molecular docking studies within the colchicine binding site of tubulin were also in good agreement with the tubulin polymerization inhibitory data and provided a basis for further structure-guided design of novel CA-4 analogues.
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: 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: Nan
authors.initials: N
authors.lastname: Jiang
authors.affiliation: Department of Pharmacology, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Qi
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: Zhaoshi
authors.initials: Z
authors.lastname: Bai
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: Dongjie
authors.initials: D
authors.lastname: Feng
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: Lei
authors.initials: L
authors.lastname: Yang
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: Mingyang
authors.initials: M
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: 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: Chang
authors.initials: C
authors.lastname: Li
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: D001632:Bibenzyls / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D001665:Binding Sites; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003078:Colchicine / Q000737:chemistry / Q000378:metabolism; D015195:Drug Design; D006801:Humans; D008299:Maleic Anhydrides / Q000737:chemistry*; D008301:Maleimides / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D008872:Microwaves; D062105:Molecular Docking Simulation; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship; D014404:Tubulin / Q000737:chemistry / Q000378:metabolism; D050257:Tubulin Modulators / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity
chemical_list: D001632:Bibenzyls; D008299:Maleic Anhydrides; D008301:Maleimides; D014404:Tubulin; D050257:Tubulin Modulators; C043592:maleimide; C040105:combretastatin; D003078:Colchicine
keywords: Anti-proliferative activity; Combretastatin A-4; Maleic anhydride; N-Substituted maleimide; Tubulin