title: Synthesis and biological evaluation of 2-aroyl-4-phenyl-5-hydroxybenzofurans as a new class of antitubulin agents.
abstract: Microtubules are among the most successful targets for development of compounds useful for anticancer therapy. Continuing our project to develop new small molecule antitumor agents, two new series of derivatives based on the 2-aroyl-4-phenylbenzofuran molecular skeleton were synthesized and evaluated for antiproliferative activity, inhibition of tubulin polymerization and cell cycle effects. SAR were elucidated with various substitutions on the benzoyl moiety at the 2-position of the benzofuran ring. The most promising compound in this series, the (5-hydroxy-4-phenylbenzofuran-2-yl)(4-methoxyphenyl)methanone derivative (3d), has significant growth inhibitory activity in the submicromolar range against the Molt4, CEM and HeLa cancer cell lines and interacts with tubulin by binding to the colchicine site. Exposure to 3d led to the arrest of K562 cells in the G2-M phase of the cell cycle and to the induction of apoptosis.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università di Ferrara, Via Fossato di Mortara 17-19, I-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: Taradas
authors.initials: T
authors.lastname: Sarkar
authors.forename: Carlota Lopez
authors.initials: CL
authors.lastname: Cara
authors.forename: Olga Cruz
authors.initials: OC
authors.lastname: Lopez
authors.forename: Maria Dora
authors.initials: MD
authors.lastname: Carrion
authors.forename: Delia
authors.initials: D
authors.lastname: Preti
authors.forename: Manlio
authors.initials: M
authors.lastname: Tolomeo
authors.forename: Jan
authors.initials: J
authors.lastname: Balzarini
authors.forename: Ernest
authors.initials: E
authors.lastname: Hamel
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D001572:Benzofurans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015195:Drug Design; D005434:Flow Cytometry; D016195:G2 Phase / Q000187:drug effects; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008870:Microtubules / Q000187:drug effects*; D014404:Tubulin / Q000096:biosynthesis / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D001572:Benzofurans; D014404:Tubulin