Synthesis and biological activities of polyquinoline derivatives: New Bcl-2 family protein modulators

Autor: Nathalie Bonnefoy, Pascale Moreau, Anne-Laure Debaud, Fabrice Anizon, Emmanuelle Saugues
Rok vydání: 2012
Předmět:
Programmed cell death
Cell Survival
bcl-X Protein
Cancer therapy
Gene Expression
Antineoplastic Agents
Peripheral blood mononuclear cell
3T3 cells
Minor Histocompatibility Antigens
Inhibitory Concentration 50
Mice
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Proto-Oncogene Proteins
Drug Discovery
medicine
Animals
Humans
bcl-2-Associated X Protein
030304 developmental biology
Pharmacology
0303 health sciences
Bh3 mimetics
Bcl-2-Like Protein 11
Cell Death
Chemistry
Organic Chemistry
Quinoline
Bcl-2 family
Membrane Proteins
3T3 Cells
General Medicine
In vitro
3. Good health
medicine.anatomical_structure
Proto-Oncogene Proteins c-bcl-2
Biochemistry
030220 oncology & carcinogenesis
Leukocytes
Mononuclear
Quinolines
Myeloid Cell Leukemia Sequence 1 Protein
Apoptosis Regulatory Proteins
Dimerization
Protein Binding
Zdroj: European Journal of Medicinal Chemistry. 57:112-125
ISSN: 0223-5234
DOI: 10.1016/j.ejmech.2012.09.012
Popis: The synthesis of quinoline derivatives, designed to interact with Bcl-x(L), and to inhibit its interaction with pro-apoptotic partners, is described and their biological effects investigated. We showed that 5 out of 28 synthetized compounds restored cell death of 3T3 cells overexpressing Bcl-x(L) following serum starvation. Active compounds were further characterized for their binding capacity to the anti-apoptotic member of the Bcl-2 family, Bcl-x(L) as well as Bcl-2, Bfl-1 and Mcl-1, and for their pro-apoptotic activities toward lymphoid tumor cells and peripheral blood mononuclear cells. Altogether our results indicate that dimeric, rather than trimeric quinoline derivatives, represent a new attractive class of BH3 mimetics for cancer therapy.
Databáze: OpenAIRE
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