RESUMO
New nitrogen-containing derivatives of betulinic and betulonic acids, hydrazides and N'-benzalhydrazides, were synthesized. Their antiviral activities toward of influenza A virus, herpes simplex type I virus, enterovirus ECHO6, and HIV-1 were studied in vitro. Betulinic acid 3-oxime was found to have the highest activity against the influenza virus. Betulonic acid, betulinic acid 4-chlorobenzalhydrazide, betulonic acid 3-oxime benzalhydrazide, and betulinic acid hydrazide inhibited the replication of herpes simplex type I virus. Betulinic acid hydrazide also showed antiviral activity toward HIV-1. All the derivatives of betulinic acid under study displayed a low antiviral activity toward enterovirus ECHO6.
Assuntos
Antivirais/química , Antivirais/farmacologia , Hidrazinas/química , Triterpenos/química , Animais , Antivirais/síntese química , Bioquímica/métodos , Células Cultivadas/virologia , Embrião de Galinha , Avaliação Pré-Clínica de Medicamentos/métodos , Enterovirus/efeitos dos fármacos , HIV-1/efeitos dos fármacos , Herpesvirus Humano 1/efeitos dos fármacos , Humanos , Hidrazinas/síntese química , Hidrazinas/farmacologia , Vírus da Influenza A/efeitos dos fármacos , Oximas/síntese química , Oximas/química , Oximas/farmacologia , Triterpenos Pentacíclicos , Relação Estrutura-Atividade , Triterpenos/farmacologia , Ácido BetulínicoRESUMO
Antiviral properties of betulin, betulinic and betulonic acids were investigated in cell cultures infected with herpes simplex type I, influenza FPV/Rostock and ECHO 6 viruses. All studied triterpenes were active against herpes simplex virus. Betulin and especially betulinic acid also suppressed ECHO 6 virus reproduction.
Assuntos
Antivirais/farmacologia , Ácido Oleanólico/análogos & derivados , Fitoterapia , Extratos Vegetais/farmacologia , Antivirais/administração & dosagem , Antivirais/uso terapêutico , Relação Dose-Resposta a Droga , Echovirus 6 Humano/efeitos dos fármacos , Herpesvirus Humano 1/efeitos dos fármacos , Humanos , Vírus da Influenza A/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Ácido Oleanólico/administração & dosagem , Ácido Oleanólico/farmacologia , Ácido Oleanólico/uso terapêutico , Triterpenos Pentacíclicos , Casca de Planta , Extratos Vegetais/administração & dosagem , Extratos Vegetais/uso terapêutico , Triterpenos/administração & dosagem , Triterpenos/farmacologia , Triterpenos/uso terapêutico , Células Tumorais Cultivadas/efeitos dos fármacos , Proteínas do Envelope Viral , Ácido BetulínicoRESUMO
PURPOSE: To characterize ocular abnormalities associated with iris atrophy in DBA/2J mice and to determine whether mice of this strain develop elevated intraocular pressure (IOP) and glaucoma. METHODS: Different approaches, including slit-lamp biomicroscopy, ophthalmoscopic examination, ultrasound backscatter microscopy, and histology were used to examine the eyes of DBA/2J mice ranging from 2 to 30 months old. IOP was measured in DBA/2J mice of different ages. RESULTS: DBA/2J mice were found to develop pigment dispersion, iris transillumination, iris atrophy, anterior synechias, and elevated IOP. IOP was elevated in most mice by the age of 9 months. These changes were followed by the death of retinal ganglion cells, optic nerve atrophy, and optic nerve cupping. The prevalence and severity of these lesions increased with age. Optic nerve atrophy and optic nerve cupping was present in the majority of mice by the age of 22 months. CONCLUSIONS: DBA/2J mice develop a progressive form of secondary angle-closure glaucoma that appears to be initiated by iris atrophy and the associated formation of synechias. This mouse strain represents a useful model to evaluate mechanisms of pressure-related ganglion cell death and optic nerve atrophy, and to evaluate strategies for neuroprotection.