title: Synthesis of triazoloquinazolinone based compounds as tubulin polymerization inhibitors and vascular disrupting agents.
abstract: A series of 1-phenyl-[1,2,4]triazolo[4,3-a]quinazolin-5-ones designed as conformationally restricted CA-4 analogues, were tested for their tubulin polymerization and growth inhibitory activities. The 3-hydroxy-4-methoxy derivatives 11d and 12d are potent inhibitors of tubulin assembly but only the N-methylated amid counterpart 12d possesses potent anticancer activity in a large panel of cancer cell lines. Upon treatment with compound 12d, remarkable cell shape changes as cell migration and tube formation were elicited in HUVECs, consistent with vasculature damaging activity.
authors.affiliation: Université de Lille, F-59000 Lille, France; Inserm UMR-S1172, Onco and NeuroChemistry, Jean-Pierre Aubert Research Center, F-59000 Lille, France.
authors.forename: Mohsine
authors.initials: M
authors.lastname: Driowya
authors.affiliation: Université de Lille, F-59000 Lille, France; Inserm UMR-S1172, Onco and NeuroChemistry, Jean-Pierre Aubert Research Center, F-59000 Lille, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Leclercq
authors.affiliation: Université de Lille, F-59000 Lille, France; Inserm UMR-S1172, Onco and NeuroChemistry, Jean-Pierre Aubert Research Center, F-59000 Lille, France.
authors.forename: Valerie
authors.initials: V
authors.lastname: Verones
authors.affiliation: Université de Lille, F-59000 Lille, France; Inserm UMR-995, Institut de Chimie Pharmaceutique Albert Lespagnol, F-59000 Lille, France.
authors.forename: Amélie
authors.initials: A
authors.lastname: Barczyk
authors.affiliation: Université de Lille, F-59000 Lille, France; UDSL, EA 7365 GRITA, 59000 Lille Cedex, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Lecoeur
authors.affiliation: Université de Lille, F-59000 Lille, France; Inserm UMR-995, Institut de Chimie Pharmaceutique Albert Lespagnol, F-59000 Lille, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Renault
authors.affiliation: Université de Lille, F-59000 Lille, France; Inserm UMR-S1172, Onco and NeuroChemistry, Jean-Pierre Aubert Research Center, F-59000 Lille, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Flouquet
authors.affiliation: Université de Lille, F-59000 Lille, France; Inserm UMR-995, Hautes Etudes Ingénieur, F-59000 Lille, France.
authors.forename: Alina
authors.initials: A
authors.lastname: Ghinet
authors.affiliation: Université de Lille, F-59000 Lille, France; Inserm UMR-S1172, Onco and NeuroChemistry, Jean-Pierre Aubert Research Center, F-59000 Lille, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Berthelot
authors.affiliation: Université de Lille, F-59000 Lille, France; Inserm UMR-S1172, Onco and NeuroChemistry, Jean-Pierre Aubert Research Center, F-59000 Lille, France. Electronic address: nicolas.lebegue@univ-lille2.fr.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Lebegue
mesh_terms: D001808:Blood Vessels / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D058105:Polymerization; D052999:Quinazolinones / Q000494:pharmacology*; D014404:Tubulin / Q000737:chemistry*; D050257:Tubulin Modulators / Q000494:pharmacology*
chemical_list: D052999:Quinazolinones; D014404:Tubulin; D050257:Tubulin Modulators
keywords: Antivascular; Combretastatin; Cytotoxicity; Triazoloquinazolinone; Tubulin polymerization