title: Synthesis, antiproliferative activity and tubulin targeting effect of acridinone and dioxophenothiazine derivatives.
abstract: The synthesis of new acridinone and dioxophenothiazine derivatives along with their tubulin polymerization inhibitory and antiproliferative activities is reported. The analysis of correlation for cytotoxic and antitubulin potential of tested compounds showed that 4-methoxyphenylethyl derivatives 18a and 19a were highly cytotoxic but were regarded to have no significant antitubulin activity. However, the introduction of a 3-hydroxy substituent leading to compounds 18e and 19e, strongly increased the antitubulin potential but was associated with a loss of the antiproliferative activity. Modeling studies, topoisomerase inhibition assays and cell cycle analysis have been performed to better investigate the mechanism of action of such compounds.
authors.affiliation: Université Lille Nord de France, Faculté des Sciences Pharmaceutiques et Biologiques, Laboratoire de Chimie Thérapeutique, EA 4481, IFR 114, 3 rue du Professeur Laguesse, BP-83, F-59006 Lille, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Verones
authors.forename: Nathalie
authors.initials: N
authors.lastname: Flouquet
authors.forename: Marie
authors.initials: M
authors.lastname: Lecoeur
authors.forename: Amelie
authors.initials: A
authors.lastname: Lemoine
authors.forename: Amaury
authors.initials: A
authors.lastname: Farce
authors.forename: Brigitte
authors.initials: B
authors.lastname: Baldeyrou
authors.forename: Christine
authors.initials: C
authors.lastname: Mahieu
authors.forename: Nicole
authors.initials: N
authors.lastname: Wattez
authors.forename: Amélie
authors.initials: A
authors.lastname: Lansiaux
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Goossens
authors.forename: Pascal
authors.initials: P
authors.lastname: Berthelot
authors.forename: Nicolas
authors.initials: N
authors.lastname: Lebegue
mesh_terms: D054831:Acridones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D016503:Drug Delivery Systems; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D015394:Molecular Structure; D010640:Phenothiazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014404:Tubulin / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D054831:Acridones; D000970:Antineoplastic Agents; D010640:Phenothiazines; D014404:Tubulin