Assuntos
Antibacterianos/química , Benzofuranos/química , Endotelinas/antagonistas & inibidores , Inibidores da Protease de HIV/química , Compostos de Espiro/química , Stachybotrys/metabolismo , Protease de HIV , Lactamas , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Estrutura Molecular , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
Six novel spirodihydrobenzofuranlactams I - VI (1 - 6) and a related spirodihydrobenzofuranalcohol, the previously described natural compound L-671,776 (7), were isolated from cultures of two different Stachybotrys species. These secondary metabolites showed antagonistic effects in the endothelin receptor binding assay and inhibited HIV-1 protease. Both biological activities are novel for L-671,776 (7). The pseudosymmetric spirodihydrobenzofuranlactam VI (6) is the most potent representative of this class of compounds exhibiting IC50 values of 1.5 microM in the ET-A receptor binding assay and 11 microM in the HIV-1 protease inhibition assay.
Assuntos
Endotelinas/antagonistas & inibidores , Fermentação , Inibidores da Protease de HIV/isolamento & purificação , Lactamas/isolamento & purificação , Stachybotrys/metabolismo , Animais , Inibidores da Protease de HIV/farmacologia , Lactamas/farmacologia , RatosAssuntos
Antraquinonas/farmacologia , Emodina/farmacologia , Inibidores Enzimáticos/farmacologia , Proteína Quinase C/antagonistas & inibidores , Proteínas Tirosina Quinases/antagonistas & inibidores , Vírus da Leucemia Murina de Abelson , Animais , Antraquinonas/isolamento & purificação , Western Blotting , Linhagem Celular Transformada , Cromatografia Líquida de Alta Pressão , Inibidores Enzimáticos/isolamento & purificação , Camundongos , Camundongos Endogâmicos BALB C , FosforilaçãoRESUMO
A new angucyclinone, named balmoralmycin (1), was isolated as an inhibitor of protein kinase C-alpha (PKC-alpha) from the Streptomyces strain P6417. Chemical screening of extracts of the same strain resulted in the detection of two decaketides with unusual structural features (2 and 3). Both compounds belong to a recently described structural class of secondary metabolites which arises from engineered biosynthesis of a recombinant Streptomyces strain. The isolation of compounds of this class from a wild-type strain has never been reported before.
Assuntos
Antraciclinas , Antibióticos Antineoplásicos/isolamento & purificação , Proteína Quinase C/antagonistas & inibidores , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/farmacologia , Benzofenonas/química , Benzofenonas/isolamento & purificação , Fermentação , Estrutura Molecular , Naftacenos/química , Naftacenos/isolamento & purificação , Pironas/química , Pironas/isolamento & purificação , Streptomyces , Relação Estrutura-AtividadeRESUMO
In the course of a screening program for HIV-1 protease inhibiting activity, six new homologues of 3-alkanoyl-5-hydroxymethyl tetronic acids (1 approximately 6) and the known natural product resistomycin (7) were isolated from cultures of the Actinomycete strain DSM 7357. The substituted tetronic acids belong to a recently described structural class of secondary metabolites. The HIV-1 activity of resistomycin (7) has not been reported before.
Assuntos
Actinomycetaceae/química , Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Furanos/isolamento & purificação , Furanos/farmacologia , Inibidores da Protease de HIV/isolamento & purificação , Inibidores da Protease de HIV/farmacologia , Antibacterianos/química , Benzopirenos/química , Benzopirenos/isolamento & purificação , Benzopirenos/farmacologia , Fermentação , Furanos/química , Inibidores da Protease de HIV/químicaAssuntos
Furanos/química , Inibidores da Protease de HIV/química , Actinomycetaceae/química , Furanos/isolamento & purificação , Furanos/farmacologia , Inibidores da Protease de HIV/isolamento & purificação , Inibidores da Protease de HIV/farmacologia , Espectroscopia de Ressonância Magnética , Espectrofotometria InfravermelhoRESUMO
N-Hydroxy-desferrioxamine B (5), a postulated metabolite of the microbial product desferrioxamine B (1), has been prepared by reduction of the intermediate oxime 6 with sodium cyanoborohydride. The oxime was obtained by selective oxidation of desferrioxamine B with hydrogen peroxide and a catalytic amount of sodium tungstate dihydrate. The iron complex derived from 5 enabled definite proof of the structure of one of four metabolites of desferrioxamine B found in urine samples of patients treated with this drug.