Aqueous extracts of marine invertebrates from Cuba coastline display neutral aminopeptidase inhibitory activities and effects on cancer cells and Plasmodium falciparum parasites

Abstract

Neutral aminopeptidases are enzymes distributed in all living organisms. By hydrolyzing biologically active peptides in tissues and biological fluids, they are involved in the control of many physiological processes. They became established targets for new therapeutic agents in cancer, but also in parasitic diseases like malaria. Marine organisms are promising sources for biomolecules but few examples of neutral aminopeptidase inhibitors are described. The goal of this work was to search in Cuban marine invertebrates, for inhibitory activities of neutral aminopeptidases of biomedical relevance, belonging to the M1 and M17 metallopeptidase families. The screening of inhibitory activities was performed using aqueous crude extracts and their 2.5 % TCA treatments. The treatments with 2.5 % TCA increased the recovery of inhibitory activities versus all enzymes tested and from all of marine species. These inhibitory activities were dose-dependent in all cases, with certain selectivity for PfA-M17 regarding hLAP, and good inhibition of hAPN. Interestingly, some TCA treated extracts displayed promising effect on either Plasmodium parasite growth as well as on PC3 and 3LL cells. This contribution is the first report identifying inhibitory activities from marine invertebrates, directed against human and malarial neutral aminopeptidases, suggesting a potential for biomedical applications for the corresponding marine species.