RESUMEN

Four ruthenium(II)-based complexes with N-(acyl)-N',N'-(disubstituted)thiourea derivatives (Th) were obtained. The compounds, with the general formula trans-[Ru(PPh3)2(Th)(bipy)]PF6, interact with bovine serum albumin (BSA) and DNA. BSA-binding constants, which were in the range of 3.3-6.5×10(4) M(-1), and the thermodynamic parameters (ΔG, ΔH and ΔS), suggest spontaneous interactions with this protein by electrostatic forces due to the positive charge of the complexes. Also, binding constant by spectrophotometric DNA titration (Kb = 0.8-1.8×10(4) M(-1)) and viscosity studies indicate weak interactions between the complexes and DNA. Cytotoxicity assays against DU-145 (prostate cancer) and A549 (lung cancer) tumour cells revealed that the complexes are more active in tumour cells than in normal (L929) cells, and that they present high cytotoxicity (low IC50 values) compared with the reference metallodrug, cisplatin.

Asunto(s)

Antineoplásicos/farmacología , Complejos de Coordinación/farmacología , Rutenio/química , Tiourea/análogos & derivados , Tiourea/farmacología , Animales , Antineoplásicos/síntesis química , Antineoplásicos/química , Bovinos , Línea Celular Tumoral , Complejos de Coordinación/síntesis química , Complejos de Coordinación/química , ADN/metabolismo , Técnicas Electroquímicas , Humanos , Ligandos , Espectroscopía de Resonancia Magnética , Conformación Molecular , Albúmina Sérica Bovina/metabolismo , Espectrometría de Fluorescencia , Espectrofotometría , Tiourea/síntesis química , Tiourea/química

RESUMEN

The rational design of anticancer drugs is one of the most promising strategies for increasing their cytotoxicity and for minimizing their toxicity. Manipulation of the structure of ligands or of complexes represents a strategy for which is possible to modify the potential mechanism of their action against the cancer cells. Here we present the cytotoxicity of some new palladium complexes and our intention is to show the importance of non-coordinated atoms of the ligands in the cytotoxicity of the complexes. New complexes of palladium (II), with general formulae [Pd(PPh3)2(L)]PF6 or [PdCl(PPh3)(L)], where L=N,N-disubstituted-N'-acyl thioureas, were synthesized and characterized by elemental analysis, molar conductivity, melting points, IR, NMR((1)H, (13)C and (31)P{(1)H}) spectroscopy. The spectroscopic data are consistent with the complexes containing an O, S chelated ligand. The structures of complexes with N,N-dimethyl-N'-benzoylthiourea, N,N-diphenyl-N'-benzoylthiourea, N,N-diethyl-N'-furoylthiourea, and N,N-diphenyl-N'-furoylthiourea were determined by X-ray crystallography, confirming the coordination of the ligands with the metal through sulfur and oxygen atoms, forming distorted square-planar structures. The N,N-disubstituted-N'-acyl thioureas and their complexes were screened with respect to their antitumor cytotoxicity against DU-145 (human prostate cancer cells), MDA-MB-231 (human breast cancer cells) and their toxicity against the L929 cell line (health cell line from mouse).

Asunto(s)

Antineoplásicos/farmacología , Complejos de Coordinación/farmacología , Citotoxinas/farmacología , Paladio/química , Tiourea/análogos & derivados , Animales , Antineoplásicos/síntesis química , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Complejos de Coordinación/síntesis química , Cristalografía por Rayos X , Citotoxinas/síntesis química , Diseño de Fármacos , Humanos , Concentración 50 Inhibidora , Ratones

RESUMEN

In the title compound, C(10)H(12)N(2)OS, the amide NCO group is twisted relative to the thio-ureido SCN(2) group, forming a dihedral angle of 55.3 (2)°. The crystal packing shows inter-molecular N-H⋯S and weak C-H⋯O inter-actions, the former giving rise to the formation of centrosymmetric R(2) (2)(8) dimers.