title: Tertiary amides with a five-membered heteroaromatic ring as new probes for the translocator protein.
abstract: 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.
authors.affiliation: Dipartimento di Chimica Farmaceutica e Tossicologica, Università di Napoli Federico II, Via D Montesano 49, 80131 Napoli, Italy. barbara.cosimelli@unina.it
authors.forename: Barbara
authors.initials: B
authors.lastname: Cosimelli
authors.forename: Francesca
authors.initials: F
authors.lastname: Simorini
authors.forename: Sabrina
authors.initials: S
authors.lastname: Taliani
authors.forename: Concettina
authors.initials: C
authors.lastname: La Motta
authors.forename: Federico
authors.initials: F
authors.lastname: Da Settimo
authors.forename: Elda
authors.initials: E
authors.lastname: Severi
authors.forename: Giovanni
authors.initials: G
authors.lastname: Greco
authors.forename: Ettore
authors.initials: E
authors.lastname: Novellino
authors.forename: Barbara
authors.initials: B
authors.lastname: Costa
authors.forename: Eleonora
authors.initials: E
authors.lastname: Da Pozzo
authors.forename: Sara
authors.initials: S
authors.lastname: Bendinelli
authors.forename: Claudia
authors.initials: C
authors.lastname: Martini
mesh_terms: D000577:Amides / Q000737:chemistry*; D045744:Cell Line, Tumor; D003500:Cyclization; D005909:Glioblastoma / Q000378:metabolism*; D006801:Humans; D015335:Molecular Probes
chemical_list: D000577:Amides; D015335:Molecular Probes