title: Synthesis and biological evaluation of 1-phenyl-1,2,3,4-dihydroisoquinoline compounds as tubulin polymerization inhibitors.
abstract: A series of 1-phenyl-3,4-dihydroisoquinoline derivatives and several 1-phenyl-1,2,3,4-tetrahydroisoquinoline, 1-phenyl-isoquinoline analogues were synthesized, and their cytotoxicity and tubulin polymerization inhibitory activity were evaluated. The 1-phenyl-3,4-dihydroisoquinoline compounds were found to be potential tubulin polymerization inhibitors. Compound 5n, bearing a 3'-OH and 4'-OCH(3) substituted 1-phenyl B-ring, was shown to confer optimal bioactivity. The single-crystal structure of 5n was further determined by X-ray diffraction, and the binding mode of 5n to tubulin was obtained by molecular docking, which can explain the structure-activity relationships. The studies presented here provide a new structural type for the development of novel antitumor agents.
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai, China.
authors.forename: Can-Hui
authors.initials: CH
authors.lastname: Zheng
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
authors.forename: Xiao-Tian
authors.initials: XT
authors.lastname: Zhou
authors.forename: Na
authors.initials: N
authors.lastname: Liu
authors.forename: Duo
authors.initials: D
authors.lastname: Shi
authors.forename: Jing-Jing
authors.initials: JJ
authors.lastname: Huang
authors.forename: Jia-Guo
authors.initials: JG
authors.lastname: Lv
authors.forename: Ju
authors.initials: J
authors.lastname: Zhu
authors.forename: You-Jun
authors.initials: YJ
authors.lastname: Zhou
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007546:Isoquinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008870:Microtubules / Q000187:drug effects*; D008958:Models, Molecular; D015394:Molecular Structure; D011485:Protein Binding; D013329:Structure-Activity Relationship; D044005:Tetrahydroisoquinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014404:Tubulin / Q000378:metabolism; D050257:Tubulin Modulators / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D007546:Isoquinolines; D044005:Tetrahydroisoquinolines; D014404:Tubulin; D050257:Tubulin Modulators; C096775:1,2,3,4-tetrahydro-1-phenylisoquinoline