title: Discovery of indolizines containing triazine moiety as new leads for the development of antitumoral agents targeting mitotic events.
abstract: A new family of 3-aroylindolizines bearing a dimethoxytriazine unit in their position 1 was designed, synthesized and evaluated for their ability to inhibit tubulin polymerization and cellular growth in vitro. Compound 39 was the best candidate in the current study with a GI50 value of 870 nM on SNB-75 CNS cancer cells and of 920 nM on MDA-MB-231/ATCC breast cancer cells. The standard NCI Compare results indicated that indolizine 39 may target PLK1 (polo-like kinase 1).
authors.affiliation: Department of Organic Chemistry, Faculty of Chemistry, 'Al. I. Cuza' University of Iasi, B-dul Carol I, Nr. 11, Corp A, 700506 Iasi, Romania.
authors.forename: Liliana
authors.initials: L
authors.lastname: Lucescu
authors.affiliation: Department of Organic Chemistry, Faculty of Chemistry, 'Al. I. Cuza' University of Iasi, B-dul Carol I, Nr. 11, Corp A, 700506 Iasi, Romania; Inserm, LIRIC-U995, Université Lille 2, CHRU de Lille, Faculté de Médecine-Pôle Recherche, Place Verdun, F-59045 Lille Cedex, France; Hautes Etudes d'Ingénieur (HEI), UCLille, Laboratoire de pharmacochimie, 13 rue de Toul, BP 41290, F-59014 Lille Cedex, France.
authors.forename: Alina
authors.initials: A
authors.lastname: Ghinet
authors.affiliation: Department of Organic Chemistry, Faculty of Chemistry, 'Al. I. Cuza' University of Iasi, B-dul Carol I, Nr. 11, Corp A, 700506 Iasi, Romania.
authors.forename: Dalila
authors.initials: D
authors.lastname: Belei
authors.affiliation: Inserm, LIRIC-U995, Université Lille 2, CHRU de Lille, Faculté de Médecine-Pôle Recherche, Place Verdun, F-59045 Lille Cedex, France; Hautes Etudes d'Ingénieur (HEI), UCLille, Laboratoire de pharmacochimie, 13 rue de Toul, BP 41290, F-59014 Lille Cedex, France.
authors.forename: Benoît
authors.initials: B
authors.lastname: Rigo
authors.affiliation: Institut de Chimie des Substances Naturelles, UPR2301 CNRS, Centre de Recherche de Gif, Avenue de la Terrasse, F-91198 Gif-sur-Yvette Cedex, France.
authors.forename: Joëlle
authors.initials: J
authors.lastname: Dubois
authors.affiliation: Department of Organic Chemistry, Faculty of Chemistry, 'Al. I. Cuza' University of Iasi, B-dul Carol I, Nr. 11, Corp A, 700506 Iasi, Romania. Electronic address: elena@uaic.ro.
authors.forename: Elena
authors.initials: E
authors.lastname: Bîcu
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007212:Indolizines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D008938:Mitosis / Q000187:drug effects*; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014227:Triazines / Q000737:chemistry* / Q000494:pharmacology; D014404:Tubulin / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D007212:Indolizines; D014227:Triazines; D014404:Tubulin
keywords: Antitumor agent; Dimethoxytriazine; Hilbert–Johnson transposition; Indolizine; O-demethylation; PLK1; Polo-like kinase 1 inhibitor