RESUMEN
Pd(II), Cu(II) and Zn(II) complexes (1-3) based on 4'-(4-(2-(piperidin-1-yl)ethoxy)phenyl)-2,2':6',2â³-terpyridine were synthesized and characterized by UV, IR, NMR, EPR, HRMS, elemental analyses, and molar conductivity measurements. The cytotoxicity of these complexes against HL-60, BGC-823, KB, Bel-7402, A549, Hela, K562 and MCF-7 cell lines in vitro was measured by MTT method. The DNA binding property of the complexes was evaluated by UV, fluorescence, CD spectroscopies and thermal denaturation. The cytotoxicity of complexes 1 and 3 against all the tested cell lines is better than that of cisplatin. Complexes 1 and 2 exhibit 7- and 4-folds higher cytotoxicity than cisplatin against Bel-7402 cell line. Complex 3 displays the highest cytotoxicity against all the cell lines tested, and shows 7-, 14-, 8-, 11- and 8-folds higher cytotoxicity than cisplatin against Bel-7402, A549, Hela, K562 and MCF-7 cell lines. The complexes bind to DNA via intercalation mode and complex 3 stabilizes the G-quadruplex. The results reveal that all the complexes display high cytotoxicity against all the tested cancer cell lines, and complex 3 is selective for G-quadruplex over duplex DNA.
Asunto(s)
Antineoplásicos/farmacología , Cobre/química , ADN de Neoplasias/efectos de los fármacos , Compuestos Organometálicos/farmacología , Paladio/química , Piperidinas/química , Piridinas/química , Zinc/química , Antineoplásicos/síntesis química , Antineoplásicos/química , Sitios de Unión/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , ADN de Neoplasias/química , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Células HL-60 , Células HeLa , Humanos , Células K562 , Células KB , Células MCF-7 , Estructura Molecular , Compuestos Organometálicos/síntesis química , Compuestos Organometálicos/química , Relación Estructura-ActividadRESUMEN
Eight novel platinum(II)/palladium(II) complexes with 1,3-dap and 4-toluensulfonyl-l-amino acid dianion, [Pt(1,3-dap)(TsalaNO)]·0.5H(2)O (1a), [Pt(1,3-dap)(TsvalNO)] (1b), [Pt(1,3-dap)(TspheNO)] (1c), [Pt(1,3-dap)(TsserNO)] (1d), [Pd(1,3-dap)(TsalaNO)]·1.5H(2)O (2a), [Pd(1,3-dap)(TsvalNO)] (2b), [Pd(1,3-dap)(TspheNO)] (2c) and [Pd(1,3-dap)(TsileNO)] (2d) have been synthesized and characterized by elemental analysis, IR, UV, (1)H NMR and mass spectrometry techniques. Crystal structure of the complex 1b has been determined by X-ray diffraction. The cytotoxicity was tested by MTT and SRB assays. The complexes (1a-1d and 2a-2d) exert cytotoxicity against Bel-7402, HL-60, KB and BGC-823, but none of them is more active than cisplatin. The results suggest that metal ions, amino acids and aliphatic N-containing ligands have effect on cytotoxicity, while the IC(50) values do not show definite correlation with variation of them.