Chiral Platinum(II) Complexes Featuring Phosphine and Chloroquine Ligands as Cytotoxic and Monofunctional DNA-Binding Agents
journal contributionposted on 21.12.2015, 00:00 by Wilmer Villarreal, Legna Colina-Vegas, Clayton Rodrigues de Oliveira, Juan C. Tenorio, Javier Ellena, Fábio C. Gozzo, Marcia Regina Cominetti, Antonio G. Ferreira, Marco Antonio Barbosa Ferreira, Maribel Navarro, Alzir A. Batista
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.
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cyclic voltammetrybioactive moleculesChinese hamster lungChloroquine Ligandscell linesabsorption spectroscopymass spectrometrychloroquine ligandstumor cell lines195 Ptmouse fibroblastschloroquine complexesanticancer drugsBSADNAfluorescence spectroscopychiral discriminationCQMCF15 NDU31 P13 CCQDPNMR spectroscopyAdditional assaysplatinum complexes