title: Carborane-conjugated 2-quinolinecarboxamide ligands of the translocator protein for boron neutron capture therapy.
abstract: Potential boron neutron capture therapy (BNCT) agents have been designed on the basis of the evidence about translocator protein (TSPO) overexpression on the outer mitochondrial membrane of tumor cells. The structure of the first TSPO ligand bearing a carborane cage (compound 2d) has been modified in order to find a suitable candidate for in vivo studies. The designed compounds were synthesized and evaluated for their potential interaction with TSPO and tumor cells. In vitro biological evaluation showed in the case of fluoromethyl derivative 4b a nanomolar TSPO affinity very similar to that of 2d, a significantly lower cytotoxicity, and a slightly superior performance as boron carrier toward breast cancer cells. Moreover, compound 4b could be used as a ¹⁹F magnetic resonance imaging (MRI) agent as well as labeled with ¹¹C or ¹⁸F to obtain positron emission tomography (PET) radiotracers in order to apply the "see and treat" strategy in BNCT.
authors.affiliation: Dipartimento Farmaco Chimico Tecnologico and European Research Centre for Drug Discovery and Development, Università degli Studi di Siena, Via A. Moro, 53100 Siena, Italy. cappelli@unisi.it
authors.forename: Andrea
authors.initials: A
authors.lastname: Cappelli
authors.forename: Salvatore
authors.initials: S
authors.lastname: Valenti
authors.forename: Alessandra
authors.initials: A
authors.lastname: Mancini
authors.forename: Germano
authors.initials: G
authors.lastname: Giuliani
authors.forename: Maurizio
authors.initials: M
authors.lastname: Anzini
authors.forename: Saverio
authors.initials: S
authors.lastname: Altieri
authors.forename: Silva
authors.initials: S
authors.lastname: Bortolussi
authors.forename: Cinzia
authors.initials: C
authors.lastname: Ferrari
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Clerici
authors.forename: Cecilia
authors.initials: C
authors.lastname: Zonta
authors.forename: Fabio
authors.initials: F
authors.lastname: Carraro
authors.forename: Irene
authors.initials: I
authors.lastname: Filippi
authors.forename: Gianluca
authors.initials: G
authors.lastname: Giorgi
authors.forename: Alessandro
authors.initials: A
authors.lastname: Donati
authors.forename: Sandra
authors.initials: S
authors.lastname: Ristori
authors.forename: Salvatore
authors.initials: S
authors.lastname: Vomero
authors.forename: Alessandra
authors.initials: A
authors.lastname: Concas
authors.forename: Giovanni
authors.initials: G
authors.lastname: Biggio
mesh_terms: D000230:Adenocarcinoma / Q000000981:diagnostic imaging / Q000473:pathology / Q000532:radiotherapy; D000818:Animals; D001665:Binding Sites; D001880:Boranes / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use; D001895:Boron / Q000737:chemistry / Q000378:metabolism; D016754:Boron Neutron Capture Therapy / Q000379:methods*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D001943:Breast Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology / Q000532:radiotherapy; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology / Q000532:radiotherapy; D018360:Crystallography, X-Ray; D005260:Female; D005462:Fluorine Radioisotopes; D015870:Gene Expression; D008279:Magnetic Resonance Imaging; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008958:Models, Molecular; D049268:Positron-Emission Tomography; D011485:Protein Binding; D011804:Quinolines / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D011963:Receptors, GABA-A / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: C530252:2-quinolinecarboxamide; D001880:Boranes; D002352:Carrier Proteins; D005462:Fluorine Radioisotopes; D011804:Quinolines; D011963:Receptors, GABA-A; C069997:Tspo protein, rat; D001895:Boron