Chiral Platinum(II) Complexes Featuring Phosphine and Chloroquine Ligands as Cytotoxic and Monofunctional DNA-Binding Agents

Chiral molecules in nature are involved
in many biological events; their selectivity and specificity make
them of great interest for understanding the behavior of bioactive
molecules, by providing information about the chiral discrimination.
Inspired by these conformational properties, we present the design
and synthesis of novel chiral platinum­(II) complexes featuring phosphine
and chloroquine ligands with the general formula [PtCl­(P)2(CQ)]­PF6 (where (P)2 = triphenylphosphine (PPh3) (5), 1,3-bis­(diphenylphosphine)­propane (dppp)
(6), 1,4-bis­(diphenylphosphine)­butane (dppb) (7), 1,1′-bis­(diphenylphosphine)­ferrocene (dppf) (8), and CQ = chloroquine] and their precursors of the type [PtCl2(P)2] are described. The complexes were characterized
by elemental analysis, absorption spectroscopy in the infrared and
ultraviolet–visible (UV-vis) regions, multinuclear (1H, 13C, 31P, 15N, and 195Pt) NMR spectroscopy, cyclic voltammetry, and mass spectrometry (in
the case of chloroquine complexes). The interactions of the new platinum–chloroquine
complexes with both albumin (BSA), using fluorescence spectroscopy,
and DNA, by four widely reported methods were also evaluated. These
experiments showed that these Pt-CQ complexes interact strongly with
DNA and have high affinities for BSA, in contrast to CQ and CQDP (chloroquine
diphosphate), which interact weakly with these biomolecules. Additional
assays were performed in order to investigate the cytotoxicity of
the platinum complexes against two healthy cell lines (mouse fibroblasts
(L929) and the Chinese hamster lung (V79-4)) and four tumor cell lines
(human breast (MDA-MB-231 and MCF-7), human lung (A549), and human
prostate (DU-145)). The results suggest that the Pt-CQ complexes are
generally more cytotoxic than the free CQ, showing that they are promising
as anticancer drugs.