title: [1,2]Oxazolo[5,4-e]isoindoles as promising tubulin polymerization inhibitors.
abstract: A series of [1,2]Oxazolo [5,4-e]isoindoles has been synthesized through a versatile and high yielding sequence. All the new structures showed in the1HNMR spectra, the typical signal in the 8.34-8.47 ppm attributable to the H-3 of the [1,2]oxazole moiety. Among all derivatives, methoxy benzyl substituents at positions 3 and 4 or/and 5 were very effective in reducing the growth of different tumor cell lines, including diffuse malignant peritoneal mesothelioma (DMPM), an uncommon and rapidly malignancy poorly responsive to available therapeutic options. The most active compound 6j was found to impair tubulin polymerization, cause cell cycle arrest at G2/M phase and induce apoptosis in DMPM cells, making it as a new lead for the discovery of new potent antimitotic drugs.
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche (STEBICEF), Università di Palermo, 90123 Palermo, Italy.
authors.forename: Virginia
authors.initials: V
authors.lastname: Spanò
authors.affiliation: Molecular Pharmacology Unit, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milano, Italy.
authors.forename: Marzia
authors.initials: M
authors.lastname: Pennati
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche (STEBICEF), Università di Palermo, 90123 Palermo, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Parrino
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche (STEBICEF), Università di Palermo, 90123 Palermo, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Carbone
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche (STEBICEF), Università di Palermo, 90123 Palermo, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Montalbano
authors.affiliation: Molecular Pharmacology Unit, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milano, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Lopergolo
authors.affiliation: Molecular Pharmacology Unit, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milano, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Zuco
authors.affiliation: Molecular Pharmacology Unit, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milano, Italy.
authors.forename: Denis
authors.initials: D
authors.lastname: Cominetti
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche (STEBICEF), Università di Palermo, 90123 Palermo, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Diana
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche (STEBICEF), Università di Palermo, 90123 Palermo, Italy.
authors.forename: Girolamo
authors.initials: G
authors.lastname: Cirrincione
authors.affiliation: Molecular Pharmacology Unit, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milano, Italy.
authors.forename: Nadia
authors.initials: N
authors.lastname: Zaffaroni
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche (STEBICEF), Università di Palermo, 90123 Palermo, Italy. Electronic address: paola.barraja@unipa.it.
authors.forename: Paola
authors.initials: P
authors.lastname: Barraja
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D054833:Isoindoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D007536:Isomerism; D059566:M Phase Cell Cycle Checkpoints / Q000187:drug effects; D055503:Protein Multimerization / Q000187:drug effects*; D020836:Protein Structure, Quaternary; D014404:Tubulin / Q000737:chemistry; D050257:Tubulin Modulators / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D054833:Isoindoles; D014404:Tubulin; D050257:Tubulin Modulators
keywords: Antitubulin agents; Diffuse malignant peritoneal mesothelioma; [1,2]Oxazolo[5,4-e]isoindoles; α-hydroxyalkyl ketones