Interactions of arene-Ru(II)-chloroquine complexes of known antimalarial and antitumor activity with human serum albumin (HSA) and transferrin

The interactions of pi-arene-Ru(II)-chloroquine complexes with human serum albumin (HSA) apotransferrin and holotransferrin have been studied by circular dichroism (CD) and UV-Visible spectroscopes together with isothermal titration calorimetry (ITC) The data for [Ru(eta(6)-p cymene)(CQ)(H2O)Cl]PF6 (1) [Ru(eta(6)-benzene) (CQ)(H2O)Cl]PF6 (2) [Ro(eta(6)-p cymene)(CQ)(H2O)(2)][PF6](2) (3) [Ru(eta(6) p-cymene)(CQ)(en)][PF6](2) (4) [Ru(eta(6) p cymene)(eta(6)-CQDP)][BF4](2) (5) (CQ chloroquine DP diphosphate en ethylenediamme) in comparison with CQDP and [Ru(eta(6)-p-cymene)(en)Cl][PF6] (6) as controls demonstrate that 1 2 3 and 5 which contain exchangeable ligands bind to HSA and to apotransferrin in a covalent manner The interaction did not affect the a-helical content in apotransferrin but resulted in a loss of this type of structure in HSA The binding was reversed in both cases by a decrease in pH and in the case of the Ru-HSA adducts also by addition of chelating agents A weaker interaction between complexes 4 and 6 and HSA was measured by ITC but was not detectable spectroscopically No interactions were observed for complexes 4 and 6 with apotransferrin or for CQDP with either protein The combined results suggest that the arene-Ru(II)-chloroquine complexes known to be active against resistant malaria and several lines of cancer cells also display a good transport behavior that makes them good candidates for drug development. (C) 2010 Elsevier Inc All rights reserved