title: Synthesis and Biological Evaluations of 1,2-Diaryl Pyrroles as Analogues of Combretastatin A-4.
abstract: A series of novel 1,2-diaryl pyrroles as analogues of combretastatin A-4 (CA-4, 1a) were synthesized and evaluated for their antitumour potential against three cancer cell lines. Most compounds exhibited growth inhibition against all of the cancer cell lines. Compound 7q not only exhibited prominent antitumour efficacy with IC50 values of 0.390 μm in SGC-7901, 0.070 μm in HT-1080 and 0.045 μm in KB cell lines but also showed low activity with IC50 values of 30.08 μm in normal L929 cell line. Moreover, compound 7q inhibited tubulin polymerization into microtubules and caused microtubule destabilization. A molecular docking study of 7q was performed to determine its binding mode at the colchicine site in the tubulin dimer.
authors.affiliation: Clinical Pharmacology Laboratory, Henan Province People's Hospital, Zhengzhou University People's Hospital, 7 Weiwu Road, Jinshui District, Zhengzhou, 450003, China.|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: Jun
authors.initials: J
authors.lastname: Sun
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: Chen
authors.affiliation: Department of Pharmacology, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang, 110016, China.
authors.forename: Chunjiang
authors.initials: C
authors.lastname: Liu
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: Zhan
authors.initials: Z
authors.lastname: Wang
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: Jiatong
authors.initials: J
authors.lastname: Pan
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.|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.
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.
authors.forename: Weige
authors.initials: W
authors.lastname: Zhang
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001665:Binding Sites; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D062105:Molecular Docking Simulation; D011758:Pyrroles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013267:Stilbenes / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014404:Tubulin / Q000737:chemistry / Q000187:drug effects; D050257:Tubulin Modulators / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D011758:Pyrroles; D013267:Stilbenes; D014404:Tubulin; D050257:Tubulin Modulators; C058728:fosbretabulin
keywords: 1,2-diaryl pyrroles; antitumour; combretastatin A-4; molecular docking study; tubulin polymerization