RESUMO
Mycestericins A, B, C, D and E were isolated from the culture broth of Mycelia sterilia ATCC 20349 along with thermozymocidin (= myriocin). Their structures were elucidated on the basis of spectroscopic studies and chemical evidence. The acetate of mycestericin C was identical with the acetate of 6,7-dihydromyriocin. Mycestericins suppressed the proliferation of lymphocytes in the mouse allogeneic mixed lymphocyte reaction, with a potency similar to that of myriocin.
Assuntos
Ácidos Eicosanoicos/isolamento & purificação , Ácidos Eicosanoicos/farmacologia , Ácidos Graxos Monoinsaturados/isolamento & purificação , Ácidos Graxos Monoinsaturados/farmacologia , Ácidos Graxos Insaturados/isolamento & purificação , Ácidos Graxos Insaturados/farmacologia , Imunossupressores/isolamento & purificação , Imunossupressores/farmacologia , Linfócitos/imunologia , Fungos Mitospóricos/metabolismo , Animais , Antifúngicos/química , Antifúngicos/isolamento & purificação , Antifúngicos/farmacologia , Divisão Celular/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Ácidos Eicosanoicos/química , Ácidos Graxos Monoinsaturados/química , Ácidos Graxos Insaturados/biossíntese , Ácidos Graxos Insaturados/química , Imunossupressores/química , Teste de Cultura Mista de Linfócitos , Linfócitos/efeitos dos fármacos , Espectroscopia de Ressonância Magnética , Camundongos , EstereoisomerismoRESUMO
A potent immunosuppressive activity was found in the culture broth of the fungus Isaria sinclairii (ATCC 24400). The metabolite, ISP-I ((2S,3R,4R)-(E)-2-amino-3,4-dihydroxy-2- hydroxymethyl-14-oxoeicos-6-enoic acid, myriocin = thermozymocidin) suppressed the proliferation of lymphocytes in mouse allogeneic mixed lymphocyte reaction, but had no effect on the growth of human tumor cell lines. It also suppressed the appearance of plaque-forming cells in response to sheep red blood cells and the generation of allo-reactive cytotoxic T lymphocytes in mice after intraperitoneal or oral administration. The metabolite was 10- to 100-fold more potent than cyclosporin A as an immunosuppressive agent of the immune response in vitro and in vivo, and appears to be a candidate for clinical application as a powerful immunosuppressant.
Assuntos
Antifúngicos/isolamento & purificação , Fungos/metabolismo , Animais , Antifúngicos/química , Antifúngicos/uso terapêutico , Ciclosporina/imunologia , Ciclosporina/farmacologia , Ácidos Graxos Monoinsaturados/química , Ácidos Graxos Monoinsaturados/isolamento & purificação , Ácidos Graxos Monoinsaturados/uso terapêutico , Fermentação , Humanos , Terapia de Imunossupressão , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Células Tumorais Cultivadas/efeitos dos fármacos , Células Tumorais Cultivadas/imunologiaRESUMO
In order to investigate the structure-activity relationships, fourteen derivatives of myriocin ((2S,3R,4R)-(E)-2-amino-3,4-dihydroxy-2-hydroxymethyl-14-oxoeicos- 6-enoic acid) were prepared and examined for immunosuppressive activity on mouse allogeneic mixed lymphocyte reaction in vitro. Among them, 14-deoxomyriocin ((2S,3R,4R)-(E)-2-amino-3,4-dihydroxy-2- hydroxymethyleicos-6-enoic acid) was the most potent. It also suppressed the generation of allo-reactive cytotoxic T lymphocytes in mice upon intraperitoneal administration, with a potency 10-fold greater than that of myriocin.
Assuntos
Antifúngicos/farmacologia , Ácidos Graxos Monoinsaturados/farmacologia , Imunossupressores/farmacologia , Animais , Antifúngicos/síntese química , Ácidos Graxos Monoinsaturados/síntese química , Fungos/metabolismo , Imunossupressores/síntese química , Teste de Cultura Mista de Linfócitos , Camundongos , Estereoisomerismo , Relação Estrutura-AtividadeRESUMO
Tochukaso is a Chinese traditional medicine composed of a fruit body of Cordyceps sinensis and its parasitic host larva. Tochukaso (C. sinensis) and the cultured mycelia of five species of Cordyceps and four species of Isaria were each extracted with hot water and examined for the inotropic effect on guinea-pig right atrium in vitro system. The extracts from C. militaris and I. felina showed a negative inotropic effect to approximately the same extent as that from Tochukaso. These three extracts also showed inhibitory action on twitch response of guinea-pig ileum and aggregation of human blood platelet. It is suggested that these activities are ascribed to the combination of adenosine, 5'-adenosine monophosphate and several other nucleic acid-related compounds, all of which have been shown to be present in the extracts.
