title: A boronic acid chalcone analog of combretastatin A-4 as a potent anti-proliferation agent.
abstract: Chalcones represent a class of natural products that inhibits tubulin assembly. In this study we designed and synthesized boronic acid analogs of chalcones in an effort to compare biological activities with combretastatin A-4, a potent inhibitor of tubulin polymerization. Systematic evaluation of the positional effects of the carbonyl moiety towards inhibition of tubulin polymerization, cancer cell proliferation and angiogenesis revealed that placement of the carbonyl adjacent to the trimethoxybenzene A-ring resulted in more active compounds than when the carbonyl group was placed adjacent to the C-ring. Our study identified a boronic acid chalcone with inhibition towards 16 human cancer cell lines in the 10-200nM range, and another three cell lines with GI(50)-values below 10nM. Furthermore, this drug has significant anti-angiogenesis effects demonstrated by HUVEC tube formation and aortic ring assay.
authors.affiliation: Department of Oncology, 3970 Reservoir Road, Drug Discovery Program, Georgetown University Medical Center, Washington, DC 20057, United States.
authors.forename: Yali
authors.initials: Y
authors.lastname: Kong
authors.forename: Kan
authors.initials: K
authors.lastname: Wang
authors.forename: Michael C
authors.initials: MC
authors.lastname: Edler
authors.forename: Ernest
authors.initials: E
authors.lastname: Hamel
authors.forename: Susan L
authors.initials: SL
authors.lastname: Mooberry
authors.forename: Mikell A
authors.initials: MA
authors.lastname: Paige
authors.forename: Milton L
authors.initials: ML
authors.lastname: Brown
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001897:Boronic Acids / Q000737:chemistry*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002599:Chalcone / Q000031:analogs & derivatives / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D042783:Endothelial Cells / Q000187:drug effects; D006801:Humans; D015394:Molecular Structure; D013237:Stereoisomerism; D013267:Stilbenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D013267:Stilbenes; D002599:Chalcone; C058728:fosbretabulin