title: Synthesis and characterization of a platinum(II) complex tethered to a ligand of the peripheral benzodiazepine receptor.
abstract: A peripheral benzodiazepine receptor (PBR) ligand (TZ6, 5) has been selected as receptor-mediated carrier for antitumor cisplatin-like compounds. Compound 5, containing a thiazole ring in position 2 of the imidazopyridine nucleus, is able to act as a dinitrogen chelate toward platinum. The resulting complex, cis-[PtCl2(5)], that is, compound 8, has been fully characterized by NMR techniques and has been shown to possess affinity and selectivity for the PBR comparable to those of 5 (IC50 of 4.6 and 2.81 nM for 8 and 5, respectively; selectivity indexes for PBR greater than 10,000 for both compounds). Hence, a platinum moiety cross-linking the imidazopyridine and the thiazole aromatic rings does not alter the affinity for PBR. The same cross-linking could be responsible for the tendency of 8 to associate in dimers. The equilibrium between monomer and dimer has been investigated by NMR spectroscopy and the corresponding constant determined.
authors.affiliation: Dipartimento Farmaco-Chimico, Università degli Studi di Bari, Via E. Orabona 4, 70125 Bari, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Margiotta
authors.forename: Rosa
authors.initials: R
authors.lastname: Ostuni
authors.forename: Rosa
authors.initials: R
authors.lastname: Ranaldo
authors.forename: Nunzio
authors.initials: N
authors.lastname: Denora
authors.forename: Valentino
authors.initials: V
authors.lastname: Laquintana
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Trapani
authors.forename: Gaetano
authors.initials: G
authors.lastname: Liso
authors.forename: Giovanni
authors.initials: G
authors.lastname: Natile
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002540:Cerebral Cortex / Q000378:metabolism; D002614:Chelating Agents / Q000737:chemistry; D019281:Dimerization; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D009944:Organoplatinum Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism*; D012996:Solutions
chemical_list: D000970:Antineoplastic Agents; D002614:Chelating Agents; D008024:Ligands; D009942:Organometallic Compounds; D009944:Organoplatinum Compounds; D011963:Receptors, GABA-A; D012996:Solutions; C518987:dichlorobis(2-(6,8-dichloro-2-(1,3-thiazol-2-yl)H-imidazo(1,2-a)pyridin-3-yl)-N,N-dipropylacetamide)platinum(II)