RESUMO
Mass-guided isolation of the dichloromethane/methanol extracts from a specimen of teleomorphic fungus of the family Cortinariaceae resulted in the identification of a new dimeric cyclobutane metabolite, achyrodimer F (1), along with the monomers hispidin (2) and bisnoryangonin (3). Their structures were determined by NMR and MS data analyses. Density Function Theory (DFT) NMR calculations was employed to confirm the chemical structure of achyrodimer F. Compound 1 inhibited tyrosyl-DNA phosphodiesterase I with an IC50 value of 1µM.
Assuntos
Agaricales/química , Ciclobutanos/farmacologia , Inibidores de Fosfodiesterase/farmacologia , Diester Fosfórico Hidrolases/metabolismo , Pironas/farmacologia , Austrália , Ciclobutanos/química , Ciclobutanos/isolamento & purificação , Relação Dose-Resposta a Droga , Humanos , Estrutura Molecular , Inibidores de Fosfodiesterase/química , Inibidores de Fosfodiesterase/isolamento & purificação , Pironas/química , Pironas/isolamento & purificação , Relação Estrutura-AtividadeRESUMO
Three new cyclic depsipeptides, neamphamides B (2), C (3), and D (4), were isolated from the Australian sponge Neamphius huxleyi. The planar structural characterization of these molecules was elucidated using 2D NMR experiments and ESI-FTICR-MS(n). Their configurations were determined by Marfey's method and J-based NMR analysis. These new metabolites inhibited the growth of human cell lines (A549, HeLa, LNCaP, PC3, and NFF) with IC(50) values ranging from 88 to 370 nM. However, neamphamide D causes A549 cell proliferation at subcytotoxic doses and should be treated cautiously as a cytotoxic compound.