RESUMO
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.
Assuntos
Antineoplásicos/farmacologia , Complexos de Coordenação/farmacologia , Rutênio/química , Tioureia/análogos & derivados , Tioureia/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Bovinos , Linhagem Celular Tumoral , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , DNA/metabolismo , Técnicas Eletroquímicas , Humanos , Ligantes , Espectroscopia de Ressonância Magnética , Conformação Molecular , Soroalbumina Bovina/metabolismo , Espectrometria de Fluorescência , Espectrofotometria , Tioureia/síntese química , Tioureia/químicaRESUMO
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).
Assuntos
Antineoplásicos/farmacologia , Complexos de Coordenação/farmacologia , Citotoxinas/farmacologia , Paládio/química , Tioureia/análogos & derivados , Animais , Antineoplásicos/síntese química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Complexos de Coordenação/síntese química , Cristalografia por Raios X , Citotoxinas/síntese química , Desenho de Fármacos , Humanos , Concentração Inibidora 50 , CamundongosRESUMO
Se estudió la actividad antitumoral del 1,3 biscloroetil nitrosourea (BCNU) sintetizado en Cuba en dos tumores transplantables de ratón, las leucemias L-1210 y P-388, así como la toxicidad de diferentes esquemas de administración del producto en ratas albinas. El producto aumentó notablemente la supervivencia de los animales tratados con respecto al control en los tumores experimentales usados y manifestó efectos tóxicos notables en el sistema hematopoyético y el hígado
Assuntos
Ratos , Animais , Feminino , Leucemia L1210/tratamento farmacológico , Leucemia P388/tratamento farmacológico , Compostos de Nitrosoureia/toxicidade , Compostos de Nitrosoureia/uso terapêutico , Transplante de NeoplasiasRESUMO
Se estudió la actividad antitumoral del 1,3 biscloroetil nitrosourea (BCNU) sintetizado en Cuba en dos tumores transplantables de ratón, las leucemias L-1210 y P-388, así como la toxicidad de diferentes esquemas de administración del producto en ratas albinas. El producto aumentó notablemente la supervivencia de los animales tratados con respecto al control en los tumores experimentales usados y manifestó efectos tóxicos notables en el sistema hematopoyético y el hígado
