title: Synthesis, Characterization, and in Vitro Evaluation of a New TSPO-Selective Bifunctional Chelate Ligand.
abstract: The 18-kDa translocator protein (TSPO) is overexpressed in many types of cancers and is also abundant in activated microglial cells occurring in inflammatory neurodegenerative diseases. Thus, TSPO has become an extremely attractive subcellular target not only for imaging disease states overexpressing this protein, but also for a selective mitochondrial drug delivery. In this work we report the synthesis, the characterization, and the in vitro evaluation of a new TSPO-selective ligand, 2-(8-(2-(bis(pyridin-2-yl)methyl)amino)acetamido)-2-(4-chlorophenyl)H-imidazo[1,2-a]pyridin-3-yl)-N,N-dipropylacetamide (CB256), which fulfils the requirements for a bifunctional chelate approach. The goal was to provide a new TSPO ligand that could be used further to prepare coordination complexes of a metallo drug to be used in diagnosis and therapy. However, the ligand itself proved to be a potent tumor cell growth inhibitor and DNA double-strand breaker.
authors.affiliation: Dipartimento di Farmacia-Scienze del Farmaco, Università degli Studi di Bari "A. Moro" , via Orabona 4, 70125 Bari, Italy.
authors.forename: Nunzio
authors.initials: N
authors.lastname: Denora
authors.affiliation: Dipartimento di Chimica, Università degli Studi di Bari "A. Moro" , via Orabona 4, 70125 Bari, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Margiotta
authors.affiliation: Dipartimento di Farmacia-Scienze del Farmaco, Università degli Studi di Bari "A. Moro" , via Orabona 4, 70125 Bari, Italy.
authors.forename: Valentino
authors.initials: V
authors.lastname: Laquintana
authors.affiliation: Dipartimento di Farmacia-Scienze del Farmaco, Università degli Studi di Bari "A. Moro" , via Orabona 4, 70125 Bari, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Lopedota
authors.affiliation: Dipartimento di Farmacia-Scienze del Farmaco, Università degli Studi di Bari "A. Moro" , via Orabona 4, 70125 Bari, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Cutrignelli
authors.affiliation: Dipartimento di Chimica, Università degli Studi di Bari "A. Moro" , via Orabona 4, 70125 Bari, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Losacco
authors.affiliation: Dipartimento di Farmacia-Scienze del Farmaco, Università degli Studi di Bari "A. Moro" , via Orabona 4, 70125 Bari, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Franco
authors.affiliation: Dipartimento di Chimica, Università degli Studi di Bari "A. Moro" , via Orabona 4, 70125 Bari, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Natile
keywords: DNA cleavage; PBR; TSPO; apoptosis; bifunctional chelate approach