Synthesis and biological activities of new di- and trimeric quinoline derivatives.
The synthesis of non-peptidic helix mimetics based on a trimeric quinoline scaffold is described. The ability of these new compounds, as well as their synthetic dimeric intermediates, to bind to various members of the Bcl-2 protein anti-apoptotic group is also evaluated. The most interesting derivative of this new series (compound A) inhibited Bcl-x(L)/Bak, Bcl-x(L)/Bax and Bcl-x(L)/Bid interactions with IC(50) values around 25 μM.
Broch
Sidonie
S
Clermont Université, Université Blaise Pascal, SEESIB, BP 10448, F-63000 Clermont-Ferrand, France.
Hénon
Hélène
H
Debaud
Anne-Laure
AL
Fogeron
Marie-Laure
ML
Bonnefoy-Bérard
Nathalie
N
Anizon
Fabrice
F
Moreau
Pascale
P
D017209:Apoptosis; D001665:Binding Sites; D019281:Dimerization; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D008958:Models, Molecular; D015394:Molecular Structure; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors* / Q000737:chemistry; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D051020:bcl-X Protein / Q000037:antagonists & inhibitors* / Q000737:chemistry
D019253:Proto-Oncogene Proteins c-bcl-2; D011804:Quinolines; D011994:Recombinant Proteins; D051020:bcl-X Protein