Mono- and dicationic Re(I)/(99m)Tc(I) tricarbonyl complexes for the targeting of energized mitochondria.

Mono- and dicationic Re(I)/(99m)Tc(I) tricarbonyl complexes for the targeting of energized mitochondria. J Inorg Biochem. 2013 Jun;123:34-45 Authors: Moura C, Mendes F, Gano L, Santos I, Paulo A Abstract The enhanced negative mitochondrial membrane potential of tumor cells can increase the cell accumulation of triphenylphosphonium (TPP) derivatives, which prompted us to investigate TPP-containing Re(I)/(99m)Tc organometallic compounds as probes for in vivo targeting of energized mitochondria. Novel compounds (Re1-Re4/Tc1-Tc4) were obtained with bifunctional chelators of the pyrazole-diamine (N,N,N-donors) and pyrazole-aminocarboxylic (N,N,O-donors) type, functionalized with TPP pharmacophores that have been introduced at the central amine of the chelators using different spacers. In this way, dicationic (Re1-Re2, Tc1-Tc2) and monocationic (Re3-Re4, Tc3-Tc4) complexes with variable lipophilicity were synthesized. The (99m)Tc complexes (Tc1-Tc4) are highly stable under physiological conditions and their chemical identification was done by HPLC comparison with the Re congeners (Re1-Re4), which were fully characterized by common analytical techniques (electrospray ionization mass spectrometry (ESI-MS), IR, multinuclear NMR). The in vitro biological evaluation of Tc1-Tc4 was performed in a panel of human tumor cell lines (PC-3, MCF-7 and H69), including cell lines overexpressing P-glycoprotein (MCF-7/MDR1 and H69/Lx4), and in isolated mitochondria....
Source: Journal of Inorganic Biochemistry - Category: Biochemistry Authors: Tags: J Inorg Biochem Source Type: research