title: Antimitotic activity of 5-hydroxy-7-methoxy-2-phenyl-4-quinolones.
abstract: We report the synthesis of 5-hydroxy-7-methoxy-2-phenyl-4-quinolones and their biological activity as antitumor agents. These molecules were initially evaluated for their ability to induce cell cycle arrest in the G2/M phase. Compounds that showed significant G2/M cell cycle arrest were tested for antiproliferative activity using both the MTT assay and the NCI in vitro 60 cell line human tumor screen. The 5-hydroxy-7-methoxy-2-phenyl-4-quinolone (3a) and 2-(3-fluorophenyl)-5-hydroxy-7-methoxy-4-quinolone (3f) were the most active in the cell cycle arrest test whereas 3f was found to be the most active in the MTT assay. In terms of structural requirements, we found that the presence of a 5-hydroxyl group, a 7-methoxy group, and an unsubstituted N1 were essential for the antimitotic activity. In accordance with the literature, a fluoro group at the 3'- or 2'-position and a methoxy or a chloro group at the 3'-position were found to be highly advantageous for both the cell cycle arrest and the antiproliferative activities.
authors.affiliation: Département de Pharmacochimie Moléculaire, UMR-CNRS 5063, Faculté de Pharmacie de Grenoble, Laboratoire de Chimie Organique, 5 avenue de Verdun, 38240 Meylan, France.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Hadjeri
authors.forename: Eva-Laure
authors.initials: EL
authors.lastname: Peiller
authors.forename: Chantal
authors.initials: C
authors.lastname: Beney
authors.forename: Nabajyoti
authors.initials: N
authors.lastname: Deka
authors.forename: Martin A
authors.initials: MA
authors.lastname: Lawson
authors.forename: Charles
authors.initials: C
authors.lastname: Dumontet
authors.forename: Ahcène
authors.initials: A
authors.lastname: Boumendjel
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D016195:G2 Phase / Q000187:drug effects; D006801:Humans; D020014:K562 Cells; D008938:Mitosis / Q000187:drug effects; D015363:Quinolones / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013778:Tetrazolium Salts / Q000378:metabolism; D013844:Thiazoles / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D015363:Quinolones; D013778:Tetrazolium Salts; D013844:Thiazoles; C022616:thiazolyl blue