RESUMEN

Complexes [Bi(2AcPh)Cl2]·0.5H2O (1), [Bi(2AcpClPh)Cl2] (2), [Bi(2AcpNO2Ph)Cl2] (3), [Bi(2AcpOHPh)Cl2]·2H2O (4), [Bi(H2BzPh)Cl3]·2H2O (5), [Bi(H2BzpClPh)Cl3] (6), [Bi(2BzpNO2Ph)Cl2]·2H2O (7) and [Bi(H2BzpOHPh)Cl3]·2H2O (8) were obtained with 2-acetylpyridine phenylhydrazone (H2AcPh), its -para-chloro-phenyl- (H2AcpClPh), -para-nitro-phenyl (H2AcpNO2Ph) and -para-hydroxy-phenyl (H2AcpOHPh) derivatives, as well as with the 2-benzoylpyridine phenylhydrazone analogues (H2BzPh, H2BzpClPh, H2BzpNO2Ph, H2BzpOHPh). Upon coordination to bismuth(III) antibacterial activity against Gram-positive and Gram-negative bacterial strains significantly improved except for complex (4). The cytotoxic effects of the compounds under study were evaluated on HL-60, Jurkat and THP-1 leukemia, and on MCF-7 and HCT-116 solid tumor cells, as well as on non-malignant Vero cells. In general, 2-acetylpyridine-derived hydrazones proved to be more potent and more selective as cytotoxic agents than the corresponding 2-benzoylpyridine-derived counterparts. Exposure of HCT-116 cells to H2AcpClPh, H2AcpNO2Ph and complex (3) led to 99% decrease of the clonogenic survival. The IC50 values of these compounds were three-fold smaller when cells were cultured in soft-agar (3D) than when cells were cultured in monolayer (2D), suggesting that they constitute interesting scaffolds, which should be considered in further studies aiming to develop new drug candidates for the treatment of colon cancer.

Asunto(s)

Antiinfecciosos/farmacología , Antiinfecciosos/toxicidad , Bacterias/efectos de los fármacos , Bismuto/química , Complejos de Coordinación/farmacología , Complejos de Coordinación/toxicidad , Hidrazonas/química , Piridinas/química , Animales , Antiinfecciosos/química , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Chlorocebus aethiops , Ensayo de Unidades Formadoras de Colonias , Complejos de Coordinación/química , Humanos , Concentración 50 Inhibidora , Neoplasias/tratamiento farmacológico , Relación Estructura-Actividad , Células Vero

RESUMEN

Complexes [Au(PyCT4BrPh)Cl]Cl (1), [Pt(PyCT4BrPh)Cl]0.5KCl (2), and [Pd(PyCT4BrPh)Cl]KCl (3) were obtained with 3-(4-bromophenyl)-1-pyridin-2-ylprop-2-en-1-one thiosemicarbazone (HPyCT4BrPh). Although complexes (2) and (3) did not exhibit potent cytotoxic activity, HPyCT4BrPh and its gold(III) complex (1) proved to be highly cytotoxic against HL-60 (human promyelocytic leukemia) and THP-1 (human monocytic leukemia) cells, and against MDA-MB 231 and MCF-7 (human breast adenocarcinoma) solid tumor cells. Except for HL-60 cells, upon coordination to gold(III) a 2- to 3-fold increase in the cytotoxic effect was observed. An investigation on the possible biological targets of the gold(III) complex was carried out. Complex (1) but not the free thiosemicarbazone inhibits the enzymatic activity of thioredoxin reductase (TrxR). The affinity of 1 for TrxR suggests metal binding to a selenol residue in the active site of the enzyme. While HPyCT4BrPh was inactive, 1 was able to inhibit topoisomerase IB (Topo IB) activity. Hence, inhibition of TrxR and Topo IB could contribute to the mechanism of cytotoxic action of complex (1).

Asunto(s)

Antineoplásicos/farmacología , Complejos de Coordinación/farmacología , ADN-Topoisomerasas de Tipo I/metabolismo , Inhibidores Enzimáticos/farmacología , Piridinas/farmacología , Reductasa de Tiorredoxina-Disulfuro/antagonistas & inhibidores , Tiosemicarbazonas/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Complejos de Coordinación/síntesis química , Complejos de Coordinación/química , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/química , Humanos , Estructura Molecular , Piridinas/síntesis química , Piridinas/química , Relación Estructura-Actividad , Reductasa de Tiorredoxina-Disulfuro/metabolismo , Tiosemicarbazonas/síntesis química , Tiosemicarbazonas/química

RESUMEN

2-Acetylpyridine acetylhydrazone (H2AcMe), 2-benzoylpyridine acetylhydrazone (H2BzMe) and complexes [Cu(H2AcMe)Cl2] (1) and [Cu(H2BzMe)Cl2] (2) were assayed for their cytotoxicity against wild type p53 U87 and mutant p53 T98 glioma cells, and against MRC-5 fibroblast cells. Compounds 1 and 2 proved to be more active than the corresponding hydrazones against U87, but not against T98 cells. Compound 1 induced higher levels of ROS than H2AcMe in both glioma cell lines. H2AcMe and 1 induced lower levels of ROS in MRC5 than in U87 cells. Compound 2 induced lower levels of ROS in MRC5 than in T98 cells. The cytotoxic effect of 1 in U87 cells could be related to its ability to provoke the release of ROS, suggesting that the cytotoxicity of 1 might be somehow p53 dependent.

Asunto(s)

Cobre/farmacología , Glioma/tratamiento farmacológico , Hidrazonas/farmacología , Especies Reactivas de Oxígeno/metabolismo , Línea Celular , Línea Celular Tumoral , Fibroblastos/efectos de los fármacos , Glioma/metabolismo , Humanos , Proteína p53 Supresora de Tumor/metabolismo

RESUMEN

New anionic complexes of lanthanide picrates containing 1-ethyl-3-methylimidazolium (EMIm) as countercation have been prepared. The Ln(III) complexes were characterized by complexometric titration, elemental analyses, infrared spectroscopy and molar conductivity. The molecular structures of the (EMIm)2[Ln(Pic)4(H2O)2]Pic complexes, Ln(III)=Sm, Eu, Gd and Tb, and Pic=picrate, were determined by X-ray crystallography. In these structures the picrate anion appears in three forms: as uncoordinated counteranion, as monodentated and bidentate ligand. The coordination polyhedron around the Ln(III) atom can be described as tricapped trigonal prismatic molecular geometry. The theoretical molecular structures of the complexes were also calculated using the Sparkle/PM3 model for Ln(III) complexes, allowing analysis of intramolecular energy transfer processes of the Eu(III) compound. The spectroscopic properties of the 4f(6) intraconfigurational transitions of the Eu(III) complex were then studied experimentally and theoretically. The low value of emission quantum efficiency of (5)D0 emitting level (η) of Eu(III) ion (ca. 10%) is due to the vibrational modes of the water molecule that act as luminescence quenching. In addition, the luminescence decay curves, the experimental intensity parameters (Ωλ), lifetimes (τ), radiative (Arad) and non-radiative (Anrad) decay rates, theoretical quantum yield (q) were also determined and discussed.

Asunto(s)

Imidazoles/química , Elementos de la Serie de los Lantanoides/química , Luminiscencia , Picratos/química , Cristalización , Cristalografía por Rayos X , Transferencia de Energía , Líquidos Iónicos , Elementos de la Serie de los Lantanoides/metabolismo , Modelos Químicos , Modelos Teóricos , Picratos/metabolismo

RESUMEN

New imidazole derived thiosemicarbazones and hydrazones were prepared by condensation of 4(5)-imidazole carboxaldehyde, 4-(1H-imidazole-1-yl)benzaldehyde and 4-(1H-imidazole-1-yl)acetophenone with a thiosemicarbazide or hydrazide. All compounds were characterized by quantitative elemental analysis, IR and NMR techniques. Eight structures were determined by single crystal X-ray diffraction. The antifungal activities of the compounds were evaluated. None of the compounds exhibited significant activity against Aspergillus flavus and Candida albicans, while 4(5)-imidazolecarboxaldehyde thiosemicarbazone (ImT) and 4-(1H-imidazole-1-yl)benzaldehyde thiosemicabazone (4ImBzT) were highly and selectively active against Cladosporium cladosporioides. 4(5)-Imidazolecarboxaldehyde benzoyl hydrazone (4(5)ImPh), 4(5)-imidazolecarboxaldehyde-para-chlorobenzoyl hydrazone (4(5)ImpClPh), 4(5)-imidazolecarboxaldehyde-para-nitrobenzoyl hydrazone (4(5)ImpNO2Ph), 4-(imidazole-1-yl)acetophenone-para-chloro-benzoyl hydrazone (4ImAcpClPh) and 4-(imidazole-1-yl)acetophenone-para-nitro-benzoylhydrazone (4ImAcpNO2Ph) were highly active against Candida glabrata. 4(5)ImpClPh and 4(5)ImpNO2Ph were very effective against C. cladosporioides. In many cases, activity was superior to that of the reference compound nystatin.

Asunto(s)

Antifúngicos/farmacología , Hidrazonas/farmacología , Imidazoles/química , Tiosemicarbazonas/farmacología , Antifúngicos/química , Aspergillus flavus/efectos de los fármacos , Candida albicans/efectos de los fármacos , Cladosporium/efectos de los fármacos , Productos Agrícolas , Hidrazonas/química , Enlace de Hidrógeno , Pruebas de Sensibilidad Microbiana , Modelos Moleculares , Conformación Molecular , Nistatina/farmacología , Enfermedades de las Plantas/microbiología , Tiosemicarbazonas/química , Difracción de Rayos X

RESUMEN

Reaction of highly soluble orally active, non-peptide antihypertensive drug losartan with copper(II) leads to the spontaneous formation of a very insoluble 2:1 covalent complex, which self assembles in a hydrophobic supramolecular structure of nanometric dimensions. Thermal analysis showed that Los/Cu(II) complex presents intermediate stability in comparison with its precursors KLos and Cu(OAc)2·H2O. Isothermal titration calorimetry indicated complexation to be a stepwise process, driven by enthalpy and entropy. Zeta potential and DLS measurements showed that it is possible to control the size and charge of nanoprecipitates by adjusting the relative concentration of Los(-) and Cu(II).

Asunto(s)

Precipitación Química , Complejos de Coordinación/química , Cobre/química , Interacciones Hidrofóbicas e Hidrofílicas , Losartán/química , Tamaño de la Partícula , Rastreo Diferencial de Calorimetría , Espectroscopía de Resonancia por Spin del Electrón , Cinética , Luz , Dinámicas no Lineales , Análisis de Regresión , Dispersión de Radiación , Solubilidad , Soluciones , Electricidad Estática , Termodinámica , Termogravimetría , Volumetría , Agua/química

RESUMEN

[Cu(HL)Cl2] complexes of chalcone-derived thiosemicarbazones were obtained with 3-phenyl-1-pyridin-2-ylprop-2-en-1-one thiosemicarbazone (HPyCTPh), complex (1), 3-(4-chlorophenyl)-1-pyridin-2-ylprop-2-en-1-one thiosemicarbazone (HPyCT4ClPh), complex (2), 3-(4-bromophenyl)-1-pyridin-2-ylprop-2-en-1-one thiosemicarbazone (HPyCT4BrPh), complex (3), and 3-(4-nitrophenyl-1-pyridin-2-ylprop-2-en-1-one thiosemicarbazone (HPyCT4NO2Ph), complex (4). 1-3 showed interaction with bovine serum albumin (BSA) and deoxyribonucleic acid from calf thymus (CT-DNA). The cytotoxic activities of the thiosemicarbazones and complexes (1-4) were tested against HL60 (wild type human promyelocytic leukemia), Jurkat (human immortalized line of T lymphocyte), MDA-MB 231 (human breast carcinoma) and HCT-116 (human colorectal carcinoma) tumor cell lineages. Upon coordination to copper(II) cytotoxicity significantly increased in Jurkat, MDA-MB 231 and HCT-116 cells. Unlike the free thiosemicarbazones, 1-4 induced DNA fragmentation in solid tumor cells indicating their pro-apoptotic potential.

Asunto(s)

Antineoplásicos/farmacología , Chalcona/química , Cobre/química , ADN/efectos de los fármacos , Compuestos Organometálicos/farmacología , Albúmina Sérica Bovina/antagonistas & inhibidores , Tiosemicarbazonas/química , Animales , Antineoplásicos/síntesis química , Antineoplásicos/química , Apoptosis/efectos de los fármacos , Sitios de Unión/efectos de los fármacos , Bovinos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , ADN/química , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Células HCT116 , Células HL-60 , Humanos , Células Jurkat , Modelos Moleculares , Estructura Molecular , Compuestos Organometálicos/síntesis química , Compuestos Organometálicos/química , Albúmina Sérica Bovina/química , Relación Estructura-Actividad

RESUMEN

Complexes [Au(2Ac4oT)Cl][AuCl2] (1), [Au(Hpy2Ac4mT)Cl2]Cl·H2O (2), [Au(Hpy2Ac4pT)Cl2]Cl (3), [Pt(H2Ac4oT)Cl]Cl (4), [Pt(2Ac4mT)Cl]·H2O (5), [Pt(2Ac4pT)Cl] (6) and [Pt(L)Cl2OH], L = 2Ac4mT (7), 2Ac4oT (8), 2Ac4pT (9) were prepared with N(4)-ortho- (H2Ac4oT), N(4)-meta- (H2Ac4mT) and N(4)-para- (H2Ac4pT) tolyl-2-acetylpyridine thiosemicarbazone. The cytotoxic activities of all compounds were assayed against U-87 and T-98 human malignant glioma cell lines. Upon coordination cytotoxicity improved in 2, 5 and 8. In general, the gold(III) complexes were more cytotoxic than those with platinum(II,IV). Several of these compounds proved to be more active than cisplatin and auranofin used as controls. The gold(III) complexes probably act by inhibiting the activity of thioredoxin reductase enzyme whereas the mode of action of the platinum(II,IV) complexes involves binding to DNA. Cells treated with the studied compounds presented morphological changes such as cell shrinkage and blebs formation, which indicate cell death by apoptosis induction.

Asunto(s)

Antineoplásicos/farmacología , Glioma/tratamiento farmacológico , Compuestos Orgánicos de Oro/química , Compuestos Orgánicos de Oro/farmacología , Compuestos Organoplatinos/química , Compuestos Organoplatinos/farmacología , Tiosemicarbazonas/química , Tiosemicarbazonas/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Muerte Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Glioma/patología , Humanos , Modelos Moleculares , Estructura Molecular , Relación Estructura-Actividad , Células Tumorales Cultivadas

RESUMEN

Six new lanthanide complexes of stoichiometric formula (C)(2)[Ln(Pic)(5)]--where (C) is a imidazolium cation coming from the ionic liquids 1-butyl-3-methylimidazolium picrate (BMIm-Pic), 1-butyl-3-ethylimidazolium picrate (BEIm-Pic), and 1,3-dibutylimidazolium picrate (BBIm-Pic), and Ln is Eu(III) or Gd(III) ions--have been prepared and characterized. To the best of our knowledge, these are the first cases of Ln(III) pentakis(picrate) complexes. The crystal structures of (BEIm)(2)[Eu(Pic)(5)] and (BBIm)(2)[Eu(Pic)(5)] compounds were determined by single-crystal X-ray diffraction. The [Eu(Pic)(5)](2-) polyhedra have nine oxygen atoms coordinated to the Eu(III) ion, four oxygen atoms from bidentate picrate, and one oxygen atom from monodentate picrate. The structures of the Eu complexes were also calculated using the sparkle model for lanthanide complexes, allowing an analysis of intramolecular energy transfer processes in the coordination compounds. The photoluminescence properties of the Eu(III) complexes were then studied experimentally and theoretically, leading to a rationalization of their emission quantum yields.

Asunto(s)

Europio/química , Imidazoles/química , Mediciones Luminiscentes , Compuestos Organometálicos/química , Compuestos Organometálicos/síntesis química , Picratos/química , Cristalografía por Rayos X , Modelos Moleculares , Estructura Molecular

RESUMEN

Complexes [Bi(2Fo4Ph)Cl(2)] (1), [Bi(2Ac4Ph)Cl(2)] (2), [Bi(2Bz4Ph)Cl(2)] (3), [Bi(H(2)Gy3DH)Cl(3)] (4), [Bi(H(2)Gy4Et)(OH)(2)Cl] (5), and [Bi(H(2)Gy4Ph)Cl(3)] (6) were prepared with pyridine-2-carbaldehyde 4-phenylthiosemicarbazone (H2Fo4Ph), 1-(pyridin-2-yl)ethanone 4-phenylthiosemicarbazone (H2Ac4Ph), phenyl(pyridin-2-yl)methanone 4-phenylthiosemicarbazone (H2Bz4Ph), as well as with glyoxaldehyde bis(thiosemicarbazone) (H(2)Gy4DH) and its 4-Et (H(2)Gy4Et) and 4-Ph (H(2)Gy4Ph) derivatives. The complexes exhibited antibacterial activities against Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, and Pseudomonas aeruginosa. Coordination to Bi(III) proved to be an effective strategy to increase the antibacterial activity of the thiosemicarbazones and bis(thiosemicarbazones).

Asunto(s)

Antibacterianos/síntesis química , Bismuto/química , Complejos de Coordinación/síntesis química , Tiosemicarbazonas/síntesis química , Antibacterianos/química , Antibacterianos/farmacología , Bacterias/efectos de los fármacos , Complejos de Coordinación/química , Complejos de Coordinación/farmacología , Cristalografía por Rayos X , Enterococcus/efectos de los fármacos , Espectroscopía de Resonancia Magnética , Pruebas de Sensibilidad Microbiana , Modelos Moleculares , Estructura Molecular , Pseudomonas aeruginosa/efectos de los fármacos , Staphylococcus aureus/efectos de los fármacos , Tiosemicarbazonas/química , Tiosemicarbazonas/farmacología

RESUMEN

N(4)-Phenyl 2-acetylpyridine thiosemicarbazone (H2Ac4Ph; N-(phenyl)-2-(1-(pyridin-2-yl)ethylidene)hydrazinecarbothioamide) and its N(4)-ortho-, -meta- and -para-fluorophenyl (H2Ac4oFPh, H2Ac4mFPh, H2Ac4pFPh), N(4)-ortho-, -meta- and -para-chlorophenyl (H2Ac4oClPh, H2Ac4mClPh, H2Ac4pClPh), N(4)-ortho-, -meta- and -para-iodophenyl (H2Ac4oIPh, H2Ac4mIPh, H2Ac4pIPh) and N(4)-ortho-, -meta- and -para-nitrophenyl (H2Ac4oNO(2)Ph, H2Ac4mNO(2)Ph, H2Ac4pNO(2)Ph) derivatives were assayed for their cytotoxicity against human malignant breast (MCF-7) and glioma (T98G and U87) cells. The compounds were highly cytotoxic against the three cell lineages (IC(50): MCF-7, 52-0.16 nM; T98G, 140-1.0 nM; U87, 160-1.4 nM). All tested thiosemicarbazones were more cytotoxic than etoposide and did not present any haemolytic activity at up to 10(-5)M. The compounds were able to induce programmed cell death. H2Ac4pClPh partially inhibited tubulin assembly at high concentrations and induced cellular microtubule disorganization.

Asunto(s)

Antineoplásicos/química , Antineoplásicos/farmacología , Tiosemicarbazonas/química , Tiosemicarbazonas/farmacología , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/patología , Apoptosis/efectos de los fármacos , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Muerte Celular/efectos de los fármacos , Línea Celular Tumoral , Neoplasias del Sistema Nervioso Central/tratamiento farmacológico , Neoplasias del Sistema Nervioso Central/patología , Cristalografía por Rayos X , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Etopósido/farmacología , Femenino , Glioblastoma/tratamiento farmacológico , Glioblastoma/genética , Glioblastoma/patología , Glioma/tratamiento farmacológico , Glioma/genética , Glioma/patología , Humanos , Concentración 50 Inhibidora , Microtúbulos/efectos de los fármacos , Estructura Molecular , Relación Estructura-Actividad , Tubulina (Proteína)/metabolismo , Proteína p53 Supresora de Tumor/genética

RESUMEN

Complexes [Sb(HAcPh)Cl(2)] (1), [Sb(HAcpClPh)Cl(2)] (2), [Sb(HAcpNO(2)Ph)Cl(2)] (3) and [Bi(HAcPh)Cl(2)] (4), [Bi(HAcpClPh)Cl(2)] (5), [Bi(HAcpNO(2)Ph)Cl(2)] (6) were obtained with 2,6-diacetylpyridine bis(benzoylhydrazone) (H(2)AcPh), 2,6-diacetylpyridine bis(para-chlorobenzoylhydrazone) (H(2)AcpClPh), and 2,6-diacetylpyridine bis(para-nitrobenzoylhydrazone) (H(2)AcpNO(2)Ph). The bis(benzoylhydrazones) were inactive as antimicrobial agents against gram-positive and gram-negative bacteria and against Candida albicans but upon coordination to antimony(III) and bismuth(III) antimicrobial activity was demonstrated. The studied compounds were tested for their cytotoxic activities against Jurkat and HL60 (leukemia), MCF-7 (breast tumor), HCT-116 (colorectal carcinoma) and peripheral blood mononuclear (PBMC) cells. All bis(benzoylhydrazones) proved to be poorly cytotoxic. Upon coordination of the bis(benzoylhydrazones) to antimony(III) and bismuth(III) cytotoxicity significantly improved. Complex (5) presented high therapeutic indexes (TI = 11-508) against all cell lineages.

Asunto(s)

Antimonio/química , Bismuto/química , Compuestos Organometálicos/química , Compuestos Organometálicos/farmacología , Piridinas/química , Animales , Antiinfecciosos/síntesis química , Antiinfecciosos/química , Antiinfecciosos/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Antineoplásicos/farmacología , Bacterias/efectos de los fármacos , Candida albicans/efectos de los fármacos , Línea Celular Tumoral , Humanos , Pruebas de Sensibilidad Microbiana , Compuestos Organometálicos/síntesis química

RESUMEN

Complexes [Au(H2Ac4DH)Cl]∙MeOH (1) [Au(H(2)2Ac4Me)Cl]Cl (2) [Au(H(2)2Ac4Ph)Cl]Cl∙2H(2)O (3) and [Au(H(2)2Bz4Ph)Cl]Cl (4) were obtained with 2-acetylpyridine thiosemicarbazone (H2Ac4DH), its N(4)-methyl (H2Ac4Me) and N(4)-phenyl (H2Ac4Ph) derivatives, as well as with N(4)-phenyl 2-benzoylpyridine thiosemicarbazone (H2Bz4Ph). The compounds were cytotoxic to Jurkat (immortalized line of T lymphocyte), HL-60 (acute myeloid leukemia), MCF-7 (human breast adenocarcinoma) and HCT-116 (colorectal carcinoma) tumor cell lines. Jurkat and HL-60 cells were more sensitive than MCF-7 and HCT-116 cells. Upon coordinating to the gold(I) metal centers in complexes (2) and (4), the cytotoxic activity of the H2Ac4Me and H2Bz4Ph ligands increased against the HL-60 and Jurkat tumor cell lines. 2 was more active than auranofin against both leukemia cells. Most of the studied compounds were less toxic than auranofin to peripheral blood mononuclear cells (PBMC). All compounds induced DNA fragmentation in HL-60 and Jurkat cells indicating their pro-apoptotic potential. Complex (2) strongly inhibited the activity of thioredoxin reductase (TrxR), which suggests inhibition of TrxR to be part of its mechanism of action.

Asunto(s)

Antineoplásicos/farmacología , Complejos de Coordinación/farmacología , Oro , Reductasa de Tiorredoxina-Disulfuro/antagonistas & inhibidores , Tiosemicarbazonas/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Auranofina/farmacología , Línea Celular Tumoral , Supervivencia Celular , Complejos de Coordinación/síntesis química , Complejos de Coordinación/química , Cristalografía por Rayos X , Fragmentación del ADN , ADN Superhelicoidal/química , Humanos , Concentración 50 Inhibidora , Leucocitos Mononucleares/efectos de los fármacos , Modelos Moleculares , Conformación Molecular , Tiosemicarbazonas/síntesis química , Tiosemicarbazonas/química

RESUMEN

[(n-Bu)Sn(2Ac4oClPh)Cl2] (1), [(n-Bu)Sn(2Ac4oFPh)Cl2] (2), [(n-Bu)Sn(2Ac4oNO2Ph)Cl2] (3), [(n-Bu)Sn(2Bz4oClPh)Cl2] (4), [(n-Bu)Sn(2Bz4oFPh)Cl2] (5) and [(n-Bu)Sn(2Bz4oNO2Ph)Cl2] (6) were obtained by reacting [(n-Bu)SnCl3] with 2-acetylpyridine-N4-orthochlorophenyl thiosemicarbazone (H2Ac4oClPh), 2-acetylpyridine-N4-orthofluorphenyl thiosemicarbazone (H2Ac4oFPh), 2-acetylpyridine-N4-orthonitrophenyl thiosemicarbazone (H2Ac4oNO2Ph), and with the corresponding 2-benzoylpyridine-derived thiosemicarbazones (H2Bz4oClPh, H2ABz4oFPh and H2Bz4oNO2Ph). The antifungal activity of the studied compounds was evaluated against several Candida species. Upon coordination of H2Bz4oNO2Ph to tin in complex (6) the antifungal activity increased three times against Candida albicans and Candida krusei and six times against Candida glabrata and Candida parapsilosis. The minimum inhibitory concentration (MIC) values of H2Ac4oNO2Ph and its complex (3) against C. albicans, C. parapsilosis and C. glabrata are similar to that of fluconazole. All studied compounds were more active than fluconazole against C. krusei.

Asunto(s)

Antifúngicos/farmacología , Candida/efectos de los fármacos , Compuestos Organometálicos/farmacología , Piridinas/química , Tiosemicarbazonas/química , Estaño/química , Antifúngicos/síntesis química , Antifúngicos/química , Cristalografía por Rayos X , Pruebas de Sensibilidad Microbiana , Modelos Moleculares , Estructura Molecular , Compuestos Organometálicos/síntesis química , Compuestos Organometálicos/química , Estereoisomerismo , Relación Estructura-Actividad