title: Studies on indolizines. Evaluation of their biological properties as microtubule-interacting agents and as melanoma targeting compounds.
abstract: With the aim of investigating new analogues of phenstatin with an indolizin-3-yl unit, in particular as the B-ring, three new series of compounds (6-8, 9-34 and 54) were synthesized and tested for interactions with tubulin polymerization and evaluated for cytotoxicity on an NCI-60 human cancer cell lines panel. The replacement of the 3'-hydroxy-4'-methoxyphenyl B-ring of phenstatin with substituted indolizine unit results in the conservation of both antitubulin and cytotoxic effect. Indolizines 9 and 17 were the most effective in the present study and showed the highest antiproliferative effect on melanoma cell lines MDA-MB-435 (GI50 = 30 nM) and could serve as new lead compounds for the development of anti-cancer therapeutics.
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; Univ Lille Nord de France, F-59000 Lille, France; UCLille, EA GRIIOT (4481), Laboratoire de pharmacochimie, HEI, 13 rue de Toul, F-59046 Lille, 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: Cristina-Maria
authors.initials: CM
authors.lastname: Abuhaie
authors.affiliation: Univ Lille Nord de France, F-59000 Lille, France; UCLille, EA GRIIOT (4481), Laboratoire de pharmacochimie, HEI, 13 rue de Toul, F-59046 Lille, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Gautret
authors.affiliation: Univ Lille Nord de France, F-59000 Lille, France; UCLille, EA GRIIOT (4481), Laboratoire de pharmacochimie, HEI, 13 rue de Toul, F-59046 Lille, 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: Univ Lille Nord de France, F-59000 Lille, France; Institut de Chimie Pharmaceutique Albert Lespagnol, EA GRIIOT (4481), IFR114, 3 Rue du Pr Laguesse, B.P. 83, F-59006 Lille, France.
authors.forename: Amaury
authors.initials: A
authors.lastname: Farce
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: 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; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007212:Indolizines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D008870:Microtubules / Q000187:drug effects*; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D007212:Indolizines
keywords: 5,6-Fused bicyclic heteroaromatic; Anticancer agent; Antitubulin; Indolizine; Melanoma; Microtubule; [3 + 2] Cycloaddition