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Artigo Acesso aberto Revisado por pares
BIBTEX RIS

Ether analogues of DPA-714 with subnanomolar affinity for the translocator protein (TSPO)

2015; Elsevier BV; Volume: 93; Linguagem: Inglês

10.1016/j.ejmech.2015.02.004

ISSN

1768-3254

Autores

Samuel D. Banister, Corinne Beinat, Shane M. Wilkinson, Bin Shen, Cecilia Bartoli, Silvia Selleri, Eleonora Da Pozzo, Claudia Martini, Frederick T. Chin, Michael Kassiou,

Tópico(s)

Cancer therapeutics and mechanisms

Resumo

Sixteen new phenyl alkyl ether derivatives (12, 14–28) of the 5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-ylacetamide (DPA) class were synthesized and evaluated in a competition binding assay against [3H]PK11195 using 18 kDa translocator protein (TSPO) derived from rat kidney mitochondrial fractions. All analogues showed superior binding affinities for TSPO compared to DPA-713 (5) and DPA-714 (6). Picomolar affinities were observed for this class of TSPO ligands in this assay for the first time, with phenethyl ether 28 showing the greatest affinity (Ki = 0.13 nM). Additionally, all analogues increased pregnenolone biosynthesis (134–331% above baseline) in a rat C6 glioma cell steroidogenesis assay.

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