title: Discovery of Novel (Imidazo[1,2-a]pyrazin-6-yl)ureas as Antiproliferative Agents Targeting P53 in Non-small Cell Lung Cancer Cell Lines.
abstract: A series of (imidazo[1,2-a]pyrazin-6-yl)ureas were synthesized through 6-aminoimidazo[1,2-a]pyrazine as a key intermediate. 1-(Imidazo[1,2-a]pyrazin-6-yl)-3-(4-methoxy - phenyl)urea displayed a cytostatic activity against a non-small cell lung cancer cell line and was chosen for further mechanistic studies. Growth kinetics highlighted a selective dose-dependent response of P53-mutant NSCLC-N6-L16 cell line and overexpression of TP53 gene induced by this compound. These pharmacological data suggest a promising reactivation of p53 mutant in NSCLC-N6-L16 cell line.
authors.affiliation: Medicinal Chemistry Department, Nantes University, Targets and Drugs for Infectious Diseases and Cancer, IICiMed EA 1155, Faculty of Pharmacy, Nantes, France.
authors.forename: Marc-Antoine
authors.initials: MA
authors.lastname: Bazin
authors.affiliation: Lung Cancer and Molecular Targets Department, Nantes University, Targets and Drugs for Infectious Diseases and Cancer, IICiMed EA 1155, Faculty of Pharmacy, Nantes, France.
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Rousseau
authors.affiliation: Medicinal Chemistry Department, Nantes University, Targets and Drugs for Infectious Diseases and Cancer, IICiMed EA 1155, Faculty of Pharmacy, Nantes, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Marhadour
authors.affiliation: Lung Cancer and Molecular Targets Department, Nantes University, Targets and Drugs for Infectious Diseases and Cancer, IICiMed EA 1155, Faculty of Pharmacy, Nantes, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Tomasoni
authors.affiliation: Medicinal Chemistry Department, Nantes University, Targets and Drugs for Infectious Diseases and Cancer, IICiMed EA 1155, Faculty of Pharmacy, Nantes, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Evenou
authors.affiliation: Medicinal Chemistry Department, Nantes University, Targets and Drugs for Infectious Diseases and Cancer, IICiMed EA 1155, Faculty of Pharmacy, Nantes, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Piessard
authors.affiliation: Department of Pharmaceutical Sciences, Laboratories of Investigation and Development, Faculty of Sciences and Philosophy, Peruvian University Cayetano Heredia, Lima, Peru.
authors.forename: Abraham J
authors.initials: AJ
authors.lastname: Vaisberg
authors.affiliation: Sorbonne Universities, Pierre and Marie Curie University Paris 06, CNRS USR3151, 'Protein Phosphorylation & Human Disease', Roscoff Biology Station, Roscoff, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Ruchaud
authors.affiliation: Sorbonne Universities, Pierre and Marie Curie University Paris 06, CNRS USR3151, 'Protein Phosphorylation & Human Disease', Roscoff Biology Station, Roscoff, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Bach
authors.affiliation: Lung Cancer and Molecular Targets Department, Nantes University, Targets and Drugs for Infectious Diseases and Cancer, IICiMed EA 1155, Faculty of Pharmacy, Nantes, France.
authors.forename: Christos
authors.initials: C
authors.lastname: Roussakis
authors.affiliation: Medicinal Chemistry Department, Nantes University, Targets and Drugs for Infectious Diseases and Cancer, IICiMed EA 1155, Faculty of Pharmacy, Nantes, France pascal.marchand@univ-nantes.fr.
authors.forename: Pascal
authors.initials: P
authors.lastname: Marchand
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D041702:BALB 3T3 Cells; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics; D051379:Mice; D011719:Pyrazines / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D014508:Urea / Q000031:analogs & derivatives* / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D007093:Imidazoles; D011719:Pyrazines; D016159:Tumor Suppressor Protein p53; D014508:Urea
keywords: Imidazo[1,2-a]pyrazine; NSCLC; antiproliferative activity; p53; urea