RESUMO
We studied the effectiveness of cyclic hydroxamic acid CHA-5 against drug-resistant and multidrug-resistant murine P388 leukemia strains. More than 60% mice receiving transplantation of rubomycin-resistant leukemia P388 strain survived after CHA-5 monotherapy; combined therapy with CHA-5 and cisplatin was also highly effective. Vincristine-resistant tumor was highly sensitive to combined treatment with CHA-5 and cyclophosphamide. It should be emphasized that standard antitumor agents were used in very low doses in combination therapy and CHA-5 significantly potentiated their effect.
Assuntos
Antineoplásicos/farmacologia , Cisplatino/farmacologia , Ciclofosfamida/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Ácidos Hidroxâmicos/farmacologia , Leucemia P388/tratamento farmacológico , Animais , Antineoplásicos/síntese química , Daunorrubicina/farmacologia , Esquema de Medicação , Combinação de Medicamentos , Sinergismo Farmacológico , Ácidos Hidroxâmicos/síntese química , Leucemia P388/mortalidade , Leucemia P388/patologia , Camundongos , Análise de Sobrevida , Vincristina/farmacologiaRESUMO
Iron-chelating activity of synthesized spirocyclic hydroxamic acids, their toxicity, and effects on mitochondrial function were studied using primary culture of cerebral cortical neurons from newborn rats. All tested compounds effectively chelated Fe(II) ions. Activity of spirocyclic hydroxamic acids more strictly depended on the structure their piperidine, but not imidazolidine fragment. All compounds were non-toxic for normal neuronal culture.