RESUMEN
Synthesis, characterization and biological studies of silver and gold complexes with 6-mercaptopurine (H2MP) are described. The Ag(I) and Au(I) complexes with HMP-, AgHMP and AuIHMP, were obtained by mixing an acidified H2MP aqueous solution with an equimolar aqueous solution of AgNO3 or Au(CN)2. The Au(III) complex with HMP-, AuIIIHMP, was obtained by adding an aqueous solution of K(AuCl4) to an acidified H2MP aqueous solution (1:1 molar ratio) and the final solution was acidified with HCl to pH=1.0. The Au(III)MP complex, KAu(MP)2, was obtained by adding an aqueous solution of K(AuCl4) to a basic H2MP solution (M:L - 1:2 molar ratio). Formulas for the complexes are: (Ag[C5H3N4S])*½H2O for AgHMP, (Au[C5H3N4S]) for AuIHMP, (Au[C5H3N4S][Cl]2)*2H2O for AuIIIHMP and K(Au[C5H2N4S]2)·2H2O for KAu(MP)2. The AuIHMP and KAu(MP)2 complexes decreased cell viability of HeLa cancer cells in vitro. The IC50 values for AuIHMP and KAu(MP)2 are 3.0 and 30.0 µM, respectively. Anti-M.tuberculosis assays showed a MIC value of 2.24 µM for AuIHMP and 5.12 µM for free MP while AgHMP is active at the concentration 93.2 µM.
Asunto(s)
Antineoplásicos/farmacología , Antituberculosos/farmacología , Complejos de Coordinación/síntesis química , Complejos de Coordinación/farmacología , Oro/química , Mercaptopurina/análogos & derivados , Plata/química , Antineoplásicos/síntesis química , Antineoplásicos/química , Antituberculosos/síntesis química , Antituberculosos/química , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Complejos de Coordinación/química , Células HeLa , Humanos , Concentración 50 Inhibidora , Yoduros/química , Mercaptopurina/síntesis química , Mercaptopurina/química , Mercaptopurina/farmacología , Mycobacterium tuberculosis/efectos de los fármacos , Compuestos Orgánicos de Oro/síntesis química , Compuestos Orgánicos de Oro/química , Compuestos Orgánicos de Oro/farmacología , Compuestos de Plata/química , Soluciones/química , Espectroscopía Infrarroja Corta/métodosRESUMEN
A series of novel 6-thiopurine derivates containing 1,2,3-triazole were synthesized and their in vivo antimalarial activity and in vitro antileishmanial activity were examined. The compounds 10, 11, 12 and 14 presented higher values of inhibition of parasite multiplication than chloroquine. For antileishmanial activity, the compound 14 showed activity against the three species of Leishmania tested. None of compounds showed cytotoxicity against mammalian cells.
Asunto(s)
Antimaláricos/química , Antiprotozoarios/química , Leishmania/efectos de los fármacos , Mercaptopurina/análogos & derivados , Plasmodium/efectos de los fármacos , Esteroides/farmacología , Triazoles/farmacología , Ácido Acético/química , Animales , Antimaláricos/síntesis química , Antimaláricos/farmacología , Antiprotozoarios/síntesis química , Antiprotozoarios/farmacología , Cloroquina/química , Femenino , Mercaptopurina/síntesis química , Mercaptopurina/química , Mercaptopurina/farmacología , Ratones , Esteroides/síntesis química , Esteroides/química , Triazoles/síntesis química , Triazoles/químicaRESUMEN
The immunological activity of macrophages against pathogens in hosts includes the phagocytosis and the production of nitric oxide. We report herein the investigation of the effect of 6-carboxymethylthiopurine on nitric oxide production by murine macrophages as well as its effect on the cell viability and proliferation after stimulus with Mycobacterium bovis bacille Calmette-Guérin, interferon-gamma or a combination of both. J774A.1 macrophages stimulated or not by bacille Calmette-Guérin (20 microg/mL), interferon-gamma or both, were cultured in the presence of 6-carboxymethylthiopurine (125, 250 and 500 microm). Nitric oxide production was measured by the Griess method and cell viability/proliferation by the diphenyltetrazolium assay [3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide]. We observed an increase of J774A.1 cell proliferation after stimulus with bacille Calmette-Guérin at 125, 250 and 500 microm (69.1, 124.0 and 89.7%, respectively) and with interferon-gamma at 125 and 250 microm (64.8% and 61.7%, respectively) (p < 0.05). In all cultures treated with 6-carboxymethylthiopurine, interferon-gamma-activated nitric oxide production by J774A.1 cells decreased as well as when subjected to interferon-gamma plus bacille Calmette-Guérin stimuli at 500 microm (p < 0.05). Altogether these data point to an anti-inflammatory effect of 6-carboxymethylthiopurine on stimulated macrophages.
Asunto(s)
Antiinflamatorios/farmacología , Macrófagos/efectos de los fármacos , Mercaptopurina/análogos & derivados , Purinas/farmacología , Animales , Línea Celular , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Activación de Macrófagos , Macrófagos/inmunología , Mercaptopurina/farmacología , Ratones , Óxido Nítrico/análisis , Óxido Nítrico/biosíntesisRESUMEN
The frequency of dental abnormalities, such as delayed dental development, microdontia, hypoplasia, agenesis, V-shaped root and shortened root was evaluated in 76 acute lymphoblastic leukemia (ALL) pediatric patients who had been off chemotherapy for 6 months. These children had been subjected to one of the three Brazilian Protocols or the BFM86 Protocol. The patients were divided into three groups: Group I (GI; high risk) treated with one of the three Brazilian Protocols who received high-dose chemotherapy, intensive maintenance and cranial radiotherapy; Group II (GII; low risk) who were also treated with one of the three Brazilian Protocols using low-intensive chemotherapy with no radiotherapy; and Group III (GIII) based on the BFM86 Protocol. Of 76 children, 13 showed no dental abnormalities (8 were at the age of tooth formation). The remaining 63 children (82.9%) showed at least one dental anomaly. The abnormalities were probably caused by the type, intensity, frequency of the treatment and age of the patients at ALL diagnosis and this might have important consequences for the children's dental development.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Irradiación Craneana/efectos adversos , Odontogénesis/efectos de los fármacos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Enfermedades Dentales/inducido químicamente , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Asparaginasa/administración & dosificación , Asparaginasa/efectos adversos , Niño , Preescolar , Terapia Combinada , Ciclofosfamida/administración & dosificación , Ciclofosfamida/efectos adversos , Citarabina/administración & dosificación , Citarabina/efectos adversos , Hipoplasia del Esmalte Dental/inducido químicamente , Dexametasona/administración & dosificación , Dexametasona/efectos adversos , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Etopósido/administración & dosificación , Etopósido/efectos adversos , Femenino , Humanos , Lactante , Masculino , Mercaptopurina/administración & dosificación , Mercaptopurina/efectos adversos , Mercaptopurina/análogos & derivados , Metotrexato/administración & dosificación , Metotrexato/efectos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/radioterapia , Prednisona/administración & dosificación , Prednisona/efectos adversos , Tenipósido/administración & dosificación , Tenipósido/efectos adversos , Anomalías Dentarias/inducido químicamente , Enfermedades Dentales/epidemiología , Erupción Dental/efectos de los fármacos , Erupción Dental/efectos de la radiación , Raíz del Diente/anomalías , Raíz del Diente/efectos de los fármacos , Raíz del Diente/efectos de la radiación , Vincristina/administración & dosificación , Vincristina/efectos adversosRESUMEN
The reaction of 16 alpha,17 alpha-epoxy-3 beta-hydroxy-5-pregnen-20-one with 6-methyl thiopurine activated with sodium hydride leads to the coupling of the purine base with the carbonyl group at C-20 to give a steroidal nucleoside analog, which is termed "nucleosteroid." In the presence of an excess of purine, a parallel reaction occurs in which the oxirane ring is opened, presumably by nucleophilic attack of an intermediate C-20 oxyanion, and yields as the main product of reaction an oligomeric mixture of nucleosteroid units linked together by ether linkages. Analogous reactions conducted with 3 beta-hydroxy-5-pregnen-20-one and with 3 beta,17 alpha-dihydroxy-5-pregnen-20-one gave minor amounts or only traces of the corresponding coupling adduct, and oligomerization did not occur. This behavior is interpreted in terms of the conformational differences showed by the different steroids to the attack by the purine.