Abstract

Peripheral benzodiazepine receptors (PBRs, also named TSPO) are overexpressed in many tumor types, with the grade of TSPO overexpression correlating with the malignancy of the tumor. For this reason, TSPO-binding ligands have been widely explored as carriers for receptor-mediated drug delivery. In this paper we have selected a ligand with nanomolar affinity for TSPO, [2-(4-chlorophenyl)-8-aminoimidazo[1,2-a]pyridin-3-yl]]-N,N-di-n-propyla cetamide (3), for preparing platinum adducts that are structural analogues to picoplatin, cis-[PtCl(2)(NH(3))(2-picoline)] (AMD0473, 6), a platinum analogue currently in advanced clinical investigation. In vitro studies assessing receptor binding and cytotoxicity against human and rat glioma cells have shown that the new compounds cis-[PtX(2)(NH(3)){[2-(4-chlorophenyl)-8-aminoimidazo[1,2-a]pyridin-3-yl ]-N,N-di-n-propylacetamidel}] (X = I,4; X = Cl, 5) keep high affinity and selectivity for TSPO (nanomolar concentration) and are as cytotoxic as cisplatin. Moreover, they appear to be equally active against sensitive and cisplatin-resistant A2780 cells. Similar to cisplatin, these compounds induce apoptosis but show a favorable 10- to 100-fold enhanced accumulation in the glioma cells.

Autore Pugliese

• Margiotta Nicola , Denora Nunzio , Laquintana Valentino

Tutti gli autori

• NATILE G.;TRAPANI G.;MARGIOTTA N.;DENORA N.;LAQUINTANA V.

Titolo volume/Rivista

Non Disponibile

Anno di pubblicazione

2010

ISSN

0022-2623

ISBN

Non Disponibile

Numero di citazioni Wos

Nessuna citazione

Ultimo Aggiornamento Citazioni

Non Disponibile

Numero di citazioni Scopus

51

Ultimo Aggiornamento Citazioni

Non Disponibile

Settori ERC

Non Disponibile

Codici ASJC

Non Disponibile