title: 4-Bromo-2-(piperidin-1-yl)thiazol-5-yl-phenyl methanone (12b) inhibits Na+/K(+)-ATPase and Ras oncogene activity in cancer cells.
abstract: The in vitro growth inhibitory activity of 26 thiazoles (including 4-halogeno-2,5-disubtituted-1,3-thiazoles) and 5 thienothiazoles was assessed on a panel of 6 human cancer cell lines, including glioma cell lines. (4-Chloro-2-(piperidin-1-yl)thiazol-5-yl)(phenyl)methanone (12a) and (4-bromo-2-(piperidin-1-yl)thiazol-5-yl)(phenyl)methanone (12b) displayed ~10 times greater in vitro growth inhibitory activity than perillyl alcohol (POH), which therapeutically benefits glioma patients through the inhibition of both alpha-1 Na(+)/K(+)-ATPase (NAK) and Ras oncogene activity. The in vitro cytostatic activities (as revealed by quantitative videomicroscopy) displayed by 12a and 12b were independent of the intrinsic resistance to pro-apoptotic stimuli associated with cancer cells. Compounds 12a and 12b displayed relatively similar inhibitory activities on purified guinea pig brain preparations that mainly express NAK alpha-2 and alpha-3 subunits, whereas only compound 12b was efficacious against purified guinea pig kidney preparations that mainly express the NAK alpha-1 subunit, which is also expressed in gliomas, melanomas and non-small-cell lung cancers NSCLCs.
authors.affiliation: Service de Neurochirurgie, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Florence
authors.initials: F
authors.lastname: Lefranc
authors.forename: Zhanjie
authors.initials: Z
authors.lastname: Xu
authors.forename: Patricia
authors.initials: P
authors.lastname: Burth
authors.forename: Véronique
authors.initials: V
authors.lastname: Mathieu
authors.forename: Germain
authors.initials: G
authors.lastname: Revelant
authors.forename: Mauro Velho
authors.initials: MV
authors.lastname: de Castro Faria
authors.forename: Caroline
authors.initials: C
authors.lastname: Noyon
authors.forename: Diogo Gomes
authors.initials: DG
authors.lastname: Garcia
authors.forename: Damien
authors.initials: D
authors.lastname: Dufour
authors.forename: Céline
authors.initials: C
authors.lastname: Bruyère
authors.forename: Cassiano Felippe
authors.initials: CF
authors.lastname: Gonçalves-de-Albuquerque
authors.forename: Pierre
authors.initials: P
authors.lastname: Van Antwerpen
authors.forename: Bernard
authors.initials: B
authors.lastname: Rogister
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Hesse
authors.forename: Gilbert
authors.initials: G
authors.lastname: Kirsch
authors.forename: Robert
authors.initials: R
authors.lastname: Kiss
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000201:enzymology; D007700:Kinetics; D061986:MCF-7 Cells; D008858:Microscopy, Phase-Contrast; D018715:Microscopy, Video; D008956:Models, Chemical; D015394:Molecular Structure; D010880:Piperidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D021122:Protein Subunits / Q000037:antagonists & inhibitors / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras) / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013844:Thiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: C584479:(4-chloro-2-(piperidin-1-yl)thiazol-5-yl)(phenyl)methanone; C584478:4-bromo-2-(piperidin-1-yl)thiazol-5-yl-phenyl methanone; D010880:Piperidines; D021122:Protein Subunits; D013844:Thiazoles; D016283:Proto-Oncogene Proteins p21(ras); D000254:Sodium-Potassium-Exchanging ATPase