Increasing the Bioavailability of RuIII Anticancer Complexes through Hydrophobic Albumin Interactions

摘要: A series of pyridine-based derivatives the clinically successful RuIII-based complexes indazolium [trans-RuCl4(1 H-indazole)2] (KP1019) and sodium (KP1339) have been synthesized to probe effect hydrophobic interactions with human serum albumin (hsA) on anticancer activity. The solution behavior protein new compounds were characterized by using electron paramagnetic resonance (EPR) UV/Vis spectroscopy. These studies revealed that incorporation substituents at 4′-position axial pyridine ligand stabilizes non-coordinate hsA. As a consequence, direct coordination is inhibited, which expected increase bioavailability complexes, thus potentially leading improved By this approach, lifetimes extended from 2 h for unsubstituted complex, more than 24 h several derivatives. Free tested their activity against SW480 colon carcinoma cell line, exhibiting low cytotoxicity. Pre-treatment hsA solubility every compound led some changes in Particularly notable was difference between methyl- dibenzyl-functionalized complexes. former shows reduced after incubation hsA, indicating due coordination. latter exhibits little its own but, following treatment exhibited significant cytotoxicity, consistent ability form protein. Overall, our demonstrate are viable target enhancing vivo.