RESUMO
EI-2128-1, a novel interleukin-1beta converting enzyme (ICE) inhibitor, was isolated from the culture broths of Penicillium sp. E-2128. EI-2128-1 selectively inhibited human recombinant ICE activity with IC50 value of 0.59 microM, without inhibiting elastase and cathepsin B. EI-2128-1 also inhibited mature interleukin-1beta secretion from THP-1 cells induced by LPS with IC50 value of 0.28 microM.
Assuntos
Inibidores de Caspase , Inibidores Enzimáticos/isolamento & purificação , Compostos de Epóxi/isolamento & purificação , Compostos de Espiro/isolamento & purificação , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Compostos de Epóxi/química , Compostos de Epóxi/farmacologia , Fermentação , Humanos , Testes de Sensibilidade Microbiana , Penicillium , Compostos de Espiro/química , Compostos de Espiro/farmacologiaRESUMO
[structure: see text] UCS1025A and B, novel pentacyclic polyketides with an unprecedented furopyrrolizidine skeleton, were isolated from the fungus Acremonium sp. KY4917. The structures and stereochemistry were elucidated by a combination of two-dimensional NMR and X-ray crystallographic analysis. UCS1025A showed unique chemical equilibria involving three tautomeric isomers and exhibited antimicrobial activity and antiproliferative activity against human tumor cell lines.
Assuntos
Acremonium/química , Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Alcaloides de Pirrolizidina/isolamento & purificação , Alcaloides de Pirrolizidina/farmacologia , Antineoplásicos/química , Linhagem Celular , Cristalografia por Raios X , Humanos , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Estrutura Molecular , Alcaloides de Pirrolizidina/químicaRESUMO
Novel halohydrin and oxime derivatives of radicicol (1) were prepared and evaluated for their v-src tyrosine kinase inhibitory, antiproliferative, and antitumor activities. Some of the resulting derivatives showed significantly improved antitumor activities than those of 1 in vitro as tested in a cell proliferation assay and in vivo using sc-inoculated human breast carcinoma and epidermoid tumor models. Design and synthesis of radicicol-based novel affinity probes are also described.
Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Lactonas/síntese química , Lactonas/farmacologia , Oximas/síntese química , Oximas/farmacologia , Antineoplásicos/farmacocinética , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Cromatografia Líquida de Alta Pressão , Ensaios de Seleção de Medicamentos Antitumorais , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/farmacologia , Feminino , Humanos , Indicadores e Reagentes , Lactonas/farmacocinética , Macrolídeos , Relação Estrutura-Atividade , Células Tumorais Cultivadas , Quinases da Família src/antagonistas & inibidoresRESUMO
Six structurally related antitumor antibiotics named GEX1 compounds were isolated from a culture broth of Streptomyces sp. GEX1A was identified as a known herbicide, herboxidiene, structurally interested by the tetrahydropyran moiety and the side chain including a conjugated diene. GEX1Q1 to approximately Q5 were determined as novel compounds related to herboxidiene. All GEX1 compounds showed cytotoxicity with IC50 values of 0.0037 to approximately 0.99 microM against human tumor cell lines in vitro, but were not active against both gram-positive and -negative bacteria. Though GEX1A/herboxidiene exhibited antitumor activity in murine tumor-planted mouse models, both GEX1Q3 and GEX1Q5 did not.
