RESUMO
Chemical and biological investigations of extracts from the sponge genus Auletta and two collections of Siphonochalina sp. have shown these organisms to be producers of the potent hemiasterlin class of antitumor agents. In addition to the previously known hemiasterlin (1) and hemiasterlin A (2), a new analogue, hemiasterlin C (3), was isolated and identified. The structures of 1 and 2 were assigned based on comparison to literature values, and 3 was identified on the basis of 1H NMR, 13C NMR, COSY, HSQC, and HMBC experiments. The cytotoxic and antitubulin activities of 1-3 were evaluated. In a comparative assay for inhibition of tubulin polymerization, the hemiasterlins were more potent than dolastatin 15 and equipotent with cryptophycin 1, but were somewhat less potent than dolastatin 10.
Assuntos
Antineoplásicos/isolamento & purificação , Oligopeptídeos/isolamento & purificação , Poríferos/química , Tubulina (Proteína)/química , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Espectroscopia de Ressonância Magnética , Oligopeptídeos/química , Oligopeptídeos/farmacologia , Células Tumorais CultivadasAssuntos
Antineoplásicos/isolamento & purificação , Poríferos/química , Quinonas/isolamento & purificação , Compostos de Espiro/isolamento & purificação , Tiazepinas , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Cromatografia Líquida de Alta Pressão , Ensaios de Seleção de Medicamentos Antitumorais , Quinonas/química , Quinonas/farmacologia , Espectrometria de Massas de Bombardeamento Rápido de Átomos , Espectrofotometria Ultravioleta , Espectroscopia de Infravermelho com Transformada de Fourier , Compostos de Espiro/química , Compostos de Espiro/farmacologia , Células Tumorais CultivadasRESUMO
The mycoparasite Humicola fuscoatra NRRL 22980 was isolated from a sclerotium of Aspergillus flavus that had been buried in a cornfield near Tifton, Ga. When grown on autoclaved rice, this fungus produced the antifungal metabolites monorden, monocillin IV, and a new monorden analog. Each metabolite produced a clear zone of inhibition surrounding paper assay disks on agar plates seeded with conidia of A. flavus. Monorden was twice as inhibitory to A. flavus mycelium extension (MIC > 28 microg/ml) as monocillin IV (MIC > 56 microg/ml). Cerebrosides C and D, metabolites known to potentiate the activity of cell wall-active antibiotics, were separated from the ethyl acetate extract but were not inhibitory to A. flavus when tested as pure compounds. This is the first report of natural products from H. fuscoatra.
Assuntos
Antifúngicos/isolamento & purificação , Ascomicetos/química , Aspergillus flavus , Cerebrosídeos/isolamento & purificação , Lactonas/isolamento & purificação , Antifúngicos/química , Antifúngicos/farmacologia , Ascomicetos/crescimento & desenvolvimento , Ascomicetos/isolamento & purificação , Cerebrosídeos/química , Cerebrosídeos/farmacologia , Lactonas/química , Lactonas/farmacologia , Macrolídeos , Testes de Sensibilidade Microbiana , Oryza/microbiologiaRESUMO
Polytolypin [1], a new pentacyclic triterpenoid exhibiting antifungal and antibiotic activity, has been isolated from cultures of Polytolypa hystricis (JS189), a fungal colonist of porcupine dung. Two known compounds [2 and 3] were also isolated. Polytolypin was obtained by chromatographic fractionation of the EtOAc extract of P. hystricis liquid cultures, and the structure was assigned on the basis of 2D nmr and hrms data.
