title: Carprofen analogues as sirtuin inhibitors: enzyme and cellular studies.
abstract: The best of both: SIRT1/2 inhibitors were developed by combining chemical features of selisistat (SIRT1-selective inhibitor; blue) and carprofen (anti-inflammatory drug; red). The most potent compound (shown) increased acetyl-p53 and acetyl-α-tubulin levels, and induced slight apoptosis at 50 μM in U937 cells, differently from selisistat and carprofen.
authors.affiliation: Istituto Pasteur-Fondazione Cenci Bolognetti, Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza Università di Roma, P.le A. Moro 5, 00185 Roma (Italy).
authors.forename: Paolo
authors.initials: P
authors.lastname: Mellini
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Carafa
authors.forename: Barbara
authors.initials: B
authors.lastname: Di Rienzo
authors.forename: Dante
authors.initials: D
authors.lastname: Rotili
authors.forename: Daniela
authors.initials: D
authors.lastname: De Vita
authors.forename: Roberto
authors.initials: R
authors.lastname: Cirilli
authors.forename: Bruno
authors.initials: B
authors.lastname: Gallinella
authors.forename: Donatella Paola
authors.initials: DP
authors.lastname: Provvisiero
authors.forename: Salvatore
authors.initials: S
authors.lastname: Di Maro
authors.forename: Ettore
authors.initials: E
authors.lastname: Novellino
authors.forename: Lucia
authors.initials: L
authors.lastname: Altucci
authors.forename: Antonello
authors.initials: A
authors.lastname: Mai
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002227:Carbazoles / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D056572:Histone Deacetylase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology*; D056564:Sirtuin 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D056565:Sirtuin 2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D002227:Carbazoles; D056572:Histone Deacetylase Inhibitors; D014404:Tubulin; D016159:Tumor Suppressor Protein p53; D056564:Sirtuin 1; D056565:Sirtuin 2; C007005:carprofen
keywords: SIRT1/2; apoptosis; histone deacetylases; inhibitors; sirtuins