title: A trifluorinated thiazoline scaffold leading to pro-apoptotic agents targeting prohibitins.
abstract: A new class of small molecules, with an unprecedented trifluorothiazoline scaffold, were synthesized and their pro-apoptotic activity was evaluated. With an EC50 in the low micromolar range, these compounds proved to be potent inducers of apoptosis in a broad spectrum of tumor cell lines, regardless of the functional status of p53. Fast structure-activity relationship studies allowed the preparation of the strongest apoptosis-inducing candidate. Using a high performance affinity purification approach, we identified prohibitins 1 and 2, key proteins involved in the maintenance of cell viability, as the targets for these compounds.
authors.affiliation: Departament de Ciències Fisiològiques II, University of Barcelona, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat (Spain).
authors.forename: Alba
authors.initials: A
authors.lastname: Pérez-Perarnau
authors.forename: Sara
authors.initials: S
authors.lastname: Preciado
authors.forename: Claudia Mariela
authors.initials: CM
authors.lastname: Palmeri
authors.forename: Cristina
authors.initials: C
authors.lastname: Moncunill-Massaguer
authors.forename: Daniel
authors.initials: D
authors.lastname: Iglesias-Serret
authors.forename: Diana M
authors.initials: DM
authors.lastname: González-Gironès
authors.forename: Miriam
authors.initials: M
authors.lastname: Miguel
authors.forename: Satoki
authors.initials: S
authors.lastname: Karasawa
authors.forename: Satoshi
authors.initials: S
authors.lastname: Sakamoto
authors.forename: Ana M
authors.initials: AM
authors.lastname: Cosialls
authors.forename: Camila
authors.initials: C
authors.lastname: Rubio-Patiño
authors.forename: José
authors.initials: J
authors.lastname: Saura-Esteller
authors.forename: Rosario
authors.initials: R
authors.lastname: Ramón
authors.forename: Laia
authors.initials: L
authors.lastname: Caja
authors.forename: Isabel
authors.initials: I
authors.lastname: Fabregat
authors.forename: Gabriel
authors.initials: G
authors.lastname: Pons
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Handa
authors.forename: Fernando
authors.initials: F
authors.lastname: Albericio
authors.forename: Joan
authors.initials: J
authors.lastname: Gil
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Lavilla
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006367:HeLa Cells; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D019169:Jurkat Cells; D015394:Molecular Structure; D000091402:Prohibitins; D012097:Repressor Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D006845:Hydrocarbons, Fluorinated; D000091402:Prohibitins; D012097:Repressor Proteins; D013844:Thiazoles
keywords: antitumor agents; drug discovery; fluorine; heterocycles; medicinal chemistry