Author(s)

Lidice González¹, Rafael E. Sánchez¹, Laritza Rojas¹, Isel Pascual¹, Rossana García-Fernández¹, María A. Chávez¹, Christian Betzel^2*

¹Centro de Estudio de Proteínas, Facultad de Biología, Universidad de La Habana, La Habana, Cuba.
²Institute of Biochemistry and Molecular Biology, Department of Chemistry, University of Hamburg, Hamburg, Germany.

Protease inhibitors have been isolated from many variable sources; however, the need to identify and characterize new molecules has increased with the discovery of new therapeutic targets and the lack of specificity of already identified compounds with inhibitory activity. The goal of this work was to search for inhibitory activity against four proteolytic enzymes already recognized as therapeutic targets: human neutrophil elastase, dipeptidyl peptidase IV, subtilisin from Bacillus licheniformis and cathepsin K in selected marine invertebrates from the Caribbean Sea. A systematic screening was carried out with selected aqueous extracts belonging to 20 species from seven different phyla: Annelida, Bryozoa, Chordata, Cnidaria, Equinodermata, Mollusca and Porifera, all collected at the coast of Havana (Cuba). All extracts showing initial inhibitory activity were characterized in terms of IC₅₀ values and specific inhibitory activity (SIA). Model enzymes were used in the case of human neutrophil elastase (porcine pancreatic elastase) and cathepsin K (papain) for the screening and all positive results were confirmed by testing toward the therapeutic targets. Ten extracts were identified showing inhibitory activity against human neutrophil elastase, for which the most promising values were obtained for Nerita peloronta. Only one extract, Bunodosoma granulifera, showed inhibitory activity against dipeptidyl peptidase IV with rather poor values of IC₅₀ and SIA. Seven extracts showed inhibitory activity against B. licheniformis subtilisin with very good IC₅₀ and SIA values for Lissodendorix isodyctialis, Cenchritis muricatus, and N. peloronta. Finally, eight extracts were positive for cathepsin K with almost similar parameters values among them. All these results confirmed the richness and potential of the marine invertebrate’s fauna and indicated new promising sources for the identification of natural compounds with potential application in therapeutics.

Target Proteases, Marine Organisms, Protease Inhibitors, Screening

González, L. , Sánchez, R. , Rojas, L. , Pascual, I. , García-Fernández, R. , Chávez, M. and Betzel, C. (2016) Screening of Protease Inhibitory Activity in Aqueous Extracts of Marine Invertebrates from Cuban Coast. American Journal of Analytical Chemistry, 7, 319-331. doi: 10.4236/ajac.2016.74030.