RESUMO
Simpotentin, a new potentiator of amphotericin B activity against Candida albicans and Cryptococcus neoformans, was isolated from the culture broth of Simplicillium minatense FKI-4981 by Diaion HP-20 column chromatography, centrifugal partition chromatography, and preparative HPLC. The structure of simpotentin was elucidated by spectroscopic analyses including NMR and MS. The compound has a mannose core to which two medium-chain fatty acids are linked. Simpotentin was found to potentiate amphotericin B activity against C. albicans by the microdilution method.
Assuntos
Anfotericina B/farmacologia , Antifúngicos/isolamento & purificação , Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Sinergismo Farmacológico , Hypocreales/metabolismo , Antifúngicos/química , Candida albicans/crescimento & desenvolvimento , Cromatografia/métodos , Cryptococcus neoformans/efeitos dos fármacos , Cryptococcus neoformans/crescimento & desenvolvimento , Meios de Cultura/química , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Testes de Sensibilidade MicrobianaRESUMO
A new compound, designated epi-trichosetin (1), was isolated along with the known compound trichosetin (2) from the culture broth of Fusarium oxysporum FKI-4553 by solvent extraction, silica gel column chromatography and reversed-phase HPLC. The structure of 1 was elucidated by comparing various spectral data with those of 2, revealing that 1 was a stereoisomer of 2. Compounds 1 and 2 inhibited the undecaprenyl pyrophosphate synthase activity of Staphylococcus aureus with IC50 values of 83 and 30 µM, respectively, and showed antimicrobial activity, particularly against Gram-positive bacteria, including methicillin-sensitive and -resistant S. aureus.
Assuntos
Alquil e Aril Transferases/antagonistas & inibidores , Inibidores Enzimáticos/farmacologia , Fusarium/química , Pirrolidinonas/farmacologia , Fracionamento Químico , Cromatografia em Gel , Cromatografia Líquida de Alta Pressão , DNA Fúngico/química , DNA Fúngico/genética , DNA Espaçador Ribossômico/química , DNA Espaçador Ribossômico/genética , Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificação , Fusarium/classificação , Fusarium/genética , Fusarium/isolamento & purificação , Bactérias Gram-Positivas/efeitos dos fármacos , Humanos , Concentração Inibidora 50 , Testes de Sensibilidade Microbiana , Modelos Moleculares , Dados de Sequência Molecular , Estrutura Molecular , Pirrolidinonas/química , Pirrolidinonas/isolamento & purificação , Análise de Sequência de DNA , Análise Espectral , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/enzimologiaRESUMO
Two new butenolides, designated trichocyalides A and B, were isolated along with the known compound harzianolide, from the culture broth of Trichoderma sp. FKI-5513 by solvent extraction, ODS column chromatography and HPLC. Their structures were elucidated by several spectral analyses, showing that they have the common skeleton of butenofuranone. Trichocyalides A and B inhibited alkaline phosphatase (ALP) activity, a typical marker enzyme of osteoblastic differentiation (IC(50): 83.0 and 187 µM, respectively), in bone morphogenetic protein (BMP)-stimulated C2C12 myoblasts mutant cells, which stably express BMP receptor activity, whereas harzianolide showed no inhibitory activity against ALP even at 500 µM.
Assuntos
Fosfatase Alcalina/antagonistas & inibidores , Butanos/isolamento & purificação , Butanos/farmacologia , Inibidores Enzimáticos/isolamento & purificação , Inibidores Enzimáticos/farmacologia , Lactonas/isolamento & purificação , Lactonas/farmacologia , Mioblastos/efeitos dos fármacos , Mioblastos/enzimologia , Trichoderma/química , Receptores de Ativinas Tipo I/antagonistas & inibidores , Receptores de Ativinas Tipo I/genética , Animais , Antibacterianos/química , Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Proteínas Morfogenéticas Ósseas/metabolismo , Proteínas Morfogenéticas Ósseas/farmacologia , Butanos/química , Linhagem Celular , Inibidores Enzimáticos/química , Genes Reporter , Lactonas/química , Camundongos , Testes de Sensibilidade Microbiana , Dados de Sequência Molecular , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Transdução de Sinais/efeitos dos fármacos , Trichoderma/classificação , Trichoderma/genéticaRESUMO
Three new beauvericins, designated beauvericins D, E and F, were isolated along with known beauvericin and beauvericin A, from the culture of Beauveria sp. FKI-1366 by solvent extraction, ODS column chromatography and HPLC. These compounds potentiate miconazole activity against not only wild Candida albicans but also fluconazole resistant C. albicans. Beauvericins D and E decreased the IC50 value of miconazole against fluconazole resistant C. albicans from 1.3 microM to 0.25 and 0.31 microM, respectively.