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

Autor(es):Mostrar menos -

Villarreal, Wilmer ^[1] ; Colina-Vegas, Legna ^[1] ; de Oliveira, Clayton Rodrigues ^[1] ; Tenorio, Juan C. ^[2] ; Ellena, Javier ^[2] ; Gozzo, Fabio C. ^[3] ; Cominetti, Marcia Regina ^[4] ; Ferreira, Antonio G. ^[1] ; Barbosa Ferreira, Marco Antonio ^[1] ; Navarro, Maribel ^[5] ; Batista, Alzir A. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Carlos UFSCar, Dept Quim, BR-13565905 Sao Carlos, SP - Brazil

^[2] Univ Sao Paulo, Inst Fis Sao Carlos, BR-13560970 Sao Carlos, SP - Brazil

^[3] Univ Estadual Campinas, UNICAMP, Inst Quim, BR-13083970 Campinas, SP - Brazil

^[4] Univ Fed Sao Carlos UFSCar, Dept Gerontol, BR-13565905 Sao Carlos, SP - Brazil

^[5] INMETRO, Inst Nacl Metrol Qualidade & Tecnol, BR-25250020 Rio De Janeiro, RJ - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Inorganic Chemistry; v. 54, n. 24, p. 11709-11720, DEC 21 2015.
• Citações Web of Science: 28

Resumo

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-bi-s(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, multinudear (H-1, C-13, P-31, N-15, and Pt-195) 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 wealdy 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 CO2. showing that they are promising as anticancer drugs. (AU)

• Processo FAPESP: 13/02311-3 - Novas abordagens na síntese assimétrica de tetraidrofuranos e tetraidropiranos substituídos com potencial aplicação na preparação de moléculas bioativas
• Beneficiário: Marco Antonio Barbosa Ferreira
• Modalidade de apoio: Auxílio à Pesquisa - Regular