[1,2]Oxazolo[5,4-e]isoindoles as promising tubulin polymerization inhibitors

6533b872fe1ef96bd12d3a42

RESEARCH PRODUCT

[1,2]Oxazolo[5,4-e]isoindoles as promising tubulin polymerization inhibitors

Denis Cominetti Patrizia Diana Marzia Pennati Alessia Lopergolo Anna Carbone Valentina Zuco Alessandra Montalbano Paola Barraja Virginia Spanò Barbara Parrino Girolamo Cirrincione Nadia Zaffaroni

subject

0301 basic medicine Cell cycle checkpoint Isoindoles 2]Oxazolo[5 Stereochemistry Diffuse malignant peritoneal mesothelioma α-hydroxyalkyl ketones Antineoplastic Agents Apoptosis Isoindoles 01 natural sciences Tubulin Polymerization Inhibitors 03 medical and health sciences chemistry.chemical_compound Isomerism Tubulin Cell Line Tumor Drug Discovery Humans Moiety Protein Structure Quaternary Oxazole [1 2]Oxazolo[5 4-e]isoindole Pharmacology 010405 organic chemistry Chemistry Antitubulin agents Drug Discovery3003 Pharmaceutical Science Organic Chemistry General Medicine Settore CHIM/08 - Chimica Farmaceutica Tubulin Modulators 0104 chemical sciences Antitubulin agent G2 Phase Cell Cycle Checkpoints α-hydroxyalkyl ketone 030104 developmental biology Apoptosis Active compound 4-e]isoindoles Proton NMR M Phase Cell Cycle Checkpoints Antitubulin agents; Diffuse malignant peritoneal mesothelioma; [1; 2]Oxazolo[5; 4-e]isoindoles; α-hydroxyalkyl ketones; Pharmacology; Drug Discovery3003 Pharmaceutical Science; Organic Chemistry [1 Drug Screening Assays Antitumor Protein Multimerization

description

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 the 1 HNMR 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.

year	journal	country	edition	language
2016-01-01

10.1016/j.ejmech.2016.09.013 http://hdl.handle.net/11567/1024131