In this study novel ligands of the translocator protein (TSPO), characterized by a five-membered aromatic heterocycle (i.e. oxazole, isoxazole, oxadiazole), a phenyl ring, and an amide side chain of carboxy or acetic type, were designed using a previously reported pharmacophore/topological model. Most of compounds showed significant TSPO binding affinity (K i values in the nanomolar/submicromolar range), the highest being displayed by oxazolacetamides 6. A number of compounds were tested for their ability to inhibit the proliferation/viability of human glioblastoma cell line U87MG. The dose-time dependent cell response to treatment with 6d demonstrated the specificity of the observed effect. The ability of 6d to induce mitochondrial membrane dissipation (ΔΨm) substantiates the intracellular pro-apoptotic mechanism activated by ligand binding to TSPO.
|Autori:||COSIMELLI B; SIMORINI F; TALIANI S; LA MOTTA C; DA SETTIMO F; SEVERI E; GRECO G; NOVELLINO E; COSTA B; DA POZZO E; BENDINELLI S; MARTINI C|
|Titolo:||Tertiary amides with a five-membered heteroaromatic ring as new probes for the translocator protein|
|Anno del prodotto:||2011|
|Digital Object Identifier (DOI):||10.1016/j.ejmech.2011.07.025|
|Appare nelle tipologie:||1.1 Articolo in rivista|