title: Design, synthesis and structure-activity relationship of 2-(3',4',5'-trimethoxybenzoyl)-benzo[b]furan derivatives as a novel class of inhibitors of tubulin polymerization.
abstract: The biological importance of microtubules in mitosis and cell division makes them an interesting target for the development of anticancer agents. Small molecules such as benzo[b]furans are attractive as inhibitors of tubulin polymerization. Thus, a new class of inhibitors of tubulin polymerization based on the 2-(3',4',5'-trimethoxybenzoyl)-benzo[b]furan molecular skeleton, with electron-donating (Me, OMe or OH) or electron-withdrawing (F, Cl and Br) substituents on the benzene ring, was synthesized and evaluated for antiproliferative activity, inhibition of tubulin polymerization and cell cycle effects. Adding a methyl group at the C-3 position resulted in increased activity. The most promising compound in this series was 2-(3',4',5'-trimethoxybenzoyl)-3-methyl-6-ethoxy-benzo[b]furan, which inhibits cancer cell growth at nanomolar concentrations and interacts strongly with tubulin by binding to the colchicine site.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università di Ferrara, Via Fossato di Mortara 17-19, 44100 Ferrara, Italy. rmr@unife.it
authors.forename: Romeo
authors.initials: R
authors.lastname: Romagnoli
authors.forename: Pier Giovanni
authors.initials: PG
authors.lastname: Baraldi
authors.forename: Maria Dora
authors.initials: MD
authors.lastname: Carrion
authors.forename: Carlota Lopez
authors.initials: CL
authors.lastname: Cara
authors.forename: Olga
authors.initials: O
authors.lastname: Cruz-Lopez
authors.forename: Manlio
authors.initials: M
authors.lastname: Tolomeo
authors.forename: Stefania
authors.initials: S
authors.lastname: Grimaudo
authors.forename: Antonietta
authors.initials: A
authors.lastname: Di Cristina
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Pipitone
authors.forename: Jan
authors.initials: J
authors.lastname: Balzarini
authors.forename: Nicola
authors.initials: N
authors.lastname: Zonta
authors.forename: Andrea
authors.initials: A
authors.lastname: Brancale
authors.forename: Ernest
authors.initials: E
authors.lastname: Hamel
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology; D001572:Benzofurans / Q000138:chemical synthesis* / Q000494:pharmacology; D001665:Binding Sites; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003078:Colchicine; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D006801:Humans; D055503:Protein Multimerization; D013329:Structure-Activity Relationship; D050257:Tubulin Modulators / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D001572:Benzofurans; D050257:Tubulin Modulators; D003078:Colchicine