Deciphering the antitumoral activity of quinacrine: Binding to and inhibition of Bcl-xL.
From the screening of a unique collection of 880 off-patent small organic molecules, we have found that quinacrine inhibits the interaction between a BH3 domain-derived peptide and the antiapoptotic protein Bcl-xL. Nuclear magnetic resonance spectroscopy confirmed that quinacrine binds to the hydrophobic groove that Bcl-xL uses for interacting with the BH3 domain of proapoptotic proteins. This activity can contribute to the anticancer activity of quinacrine.
Orzáez
Mar
M
Department of Medicinal Chemistry. Centro de Investigación Príncipe Felipe, Av. Autopista del Saler, 16. E-46012 Valencia, Spain.
Mondragón
Laura
L
García-Jareño
Alicia
A
Mosulén
Silvia
S
Pineda-Lucena
Antonio
A
Pérez-Payá
Enrique
E
D000166:Acridines / Q000737:chemistry; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis; D002626:Chemistry, Pharmaceutical / Q000379:methods; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D020128:Inhibitory Concentration 50; D019169:Jurkat Cells; D015394:Molecular Structure; D011485:Protein Binding; D011796:Quinacrine / Q000737:chemistry / Q000494:pharmacology*; D013050:Spectrometry, Fluorescence / Q000379:methods; D051028:bcl-2-Associated X Protein / Q000737:chemistry; D051020:bcl-X Protein / Q000737:chemistry*
D000166:Acridines; D000970:Antineoplastic Agents; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D011796:Quinacrine