title: Synthesis of macrocyclic bisbibenzyl derivatives and their anticancer effects as anti-tubulin agents.
abstract: Based on the core skeleton of the total synthesized bisbibenzyl marchantin C, riccardin D and plagiochin E, a series of brominated and aminomethylated derivatives of above three bisbibenzyls have been synthesized and their cytotoxic activity against KB, MCF-7 and PC3 cell lines has been preliminary evaluated. The bio-test results revealed that the brominated derivatives 21, 22, 24, 25 and 28 exhibited excellent antiproliferative activity, with IC(50) value lower than their parent compounds. As a most potent microtubule depolymerization agent, compound 28 was found to arrest cells at the G(2)/M phase of the cell cycle as determined by the flow cytometry assay in PC3 cell line. The remarkable biological profile and novel structure of these bisbibenzyl derivatives make them possible as promising candidates for clinical development as chemotherapeutic agents.
authors.affiliation: School of Pharmaceutical Sciences, Shandong University, Jinan 250012, PR China.
authors.forename: Juan
authors.initials: J
authors.lastname: Jiang
authors.forename: Bin
authors.initials: B
authors.lastname: Sun
authors.forename: Yan-yan
authors.initials: YY
authors.lastname: Wang
authors.forename: Min
authors.initials: M
authors.lastname: Cui
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Chang-zhi
authors.initials: CZ
authors.lastname: Cui
authors.forename: Yan-feng
authors.initials: YF
authors.lastname: Wang
authors.forename: Xi-gong
authors.initials: XG
authors.lastname: Liu
authors.forename: Hong-xiang
authors.initials: HX
authors.lastname: Lou
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; D004354:Drug Screening Assays, Antitumor; D059565:G2 Phase Cell Cycle Checkpoints; D006801:Humans; D047028:Macrocyclic Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D056004:Molecular Dynamics Simulation; D017434:Protein Structure, Tertiary; D014404:Tubulin / Q000737:chemistry* / Q000378:metabolism; D050257:Tubulin Modulators / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D047028:Macrocyclic Compounds; D014404:Tubulin; D050257:Tubulin Modulators