Anti-HCV protease of diketopiperazines produced by the Red Sea sponge-associated fungus Aspergillus versicolor

Hepatitis C virus (HCV) infection is a global problem due to the difficulties in developing a protective vaccine. In this work, we demonstrated that the ethyl acetate extract of the endophytic fungus Aspergillus versicolor exhibited significant activity against HCV NS3/4A protease with IC50 value of 30 μg/mL. The fungus was isolated from the Red Sea black sponge Spongia officinalis and identified by its morphology and 18S rDNA. Large-scale fermentation of the fungus followed by chromatographic purification with silica gel, Sephadex LH-20 and semipreparative HPLC of the active extract led to isolation of some known metabolites related to cyclodipeptides and the so-called diketopiperazines (DKPs). The DKP, cyclo(L-Tyr-L-Pro), displayed strong effect as HCV protease inhibitor with IC50 value of 8.2 μg/mL. A computational docking study of cyclo(L-Tyr-L-Pro) against HCV protease was used to formulate a hypothetical mechanism for the inhibitory activity of the active compound on the tested enzyme.<br/

Antarctic marine chemical ecology: what is next?

71 páginas, 1 tabla, 3 figuras.Antarctic ecosystems are exposed to unique environmental characteristics resulting in communities structured both by biotic interactions such as predation and competition, as well as abiotic factors such as seasonality and ice-scouring. It is important to understand how ecological factors may trigger chemical mechanisms in marine Antarctic organisms as a response for survival. However, very little is known yet about the evolution of chemical compounds in Antarctic organisms. Investigations in chemical ecology have demonstrated over the last several years that defensive metabolites have evolved in numerous representative Antarctic species. This contradicts earlier theories concerning biogeographic variation in predation and chemical defenses. As reviewed here, a number of interesting natural products have been isolated from Antarctic organisms. However, we believe many more are still to be discovered. Currently, many groups such as microorganisms, planktonic organisms and deepsea fauna remain almost totally unknown regarding their natural products. Furthermore, for many described compounds, ecological roles have yet to be evaluated. In fact, much of the research carried out to date has been conducted in the laboratory, and only in a few cases in an ecologically relevant context. Therefore, there is a need to extend the experiments to the field, as done in tropical and temperate marine ecosystems, or at least, to test the activity of the chemicals in natural conditions and ecologically meaningful interactions. Defense against predators is always one of the main topics when talking about the roles of natural products in species interactions, but many other interesting aspects, such as competition, chemoattraction, fouling avoidance and ultraviolet (UV) protection, also deserve further attention. In our opinion, challenging future developments are to be expected for Antarctic marine chemical ecology in the years to come.This work would not have been possible without the financial support of the Ministry of Science and Education of Spain through different grants along recent years in the general frame of our ECOQUIM projects (ANT97-1590-E, ANT97-0273, REN2002-12006-E ⁄ANT, REN2003-00545 and CGL2004- 03356 ⁄ANT).Peer reviewe