info:eu-repo/semantics/article
Antiparasitic effect of a fraction enriched in tight-binding protease inhibitors isolated from the Caribbean coral Plexaura homomalla
Registro en:
Salas Sarduy, Emir; Cabrera Muñoz, Aymara; Cauerff, Ana Albina; González González, Yamile ; Trejo, Sebastian Alejandro; et al.; Antiparasitic effect of a fraction enriched in tight-binding protease inhibitors isolated from the Caribbean coral Plexaura homomalla; Elsevier; Experimental Parasitology; 135; 3; 30-9-2013; 611-622
0014-4894
Autor
Salas Sarduy, Emir
Cabrera Muñoz, Aymara
Cauerff, Ana Albina
González González, Yamile
Trejo, Sebastian Alejandro
Chidichimo, Agustina
Chávez Planes, Maria de Los Angeles
Cazzulo, Juan Jose
Resumen
Malaria and American Trypanosomiasis constitute major global health problems. The continued emergence and spreading of resistant strains and the limited efficacy and/or safety of currently available therapeutic agents require a constant search for new sources of antiparasitic compounds. In the present study, a fraction enriched in tight-binding protease inhibitors was isolated from the Caribbean coral Plexaura homomalla (Esper, 1792), functionally characterized and tested for their antiparasitic activity against Trypanosoma cruzi and Plasmodium falciparum. The resultant fraction was chromatographically enriched in tight-binding inhibitors active against Papain-like cysteine peptidases (92%) and Pepsin-like aspartyl peptidases (8%). Globally, the inhibitors present in the enriched fraction showed no competition with substrates and apparent Ki values of 1.99 and 4.81 nM for Falcipain 2 and Cruzipain, the major cysteine peptidases from P. falciparum and T. cruzi, respectively. The inhibitor-enriched fraction showed promising antiparasitic activity in cultures. It reduced the growth of the chloroquine-resistant P. falciparum strain Dd2 (IC50 = 0.46 μM) and promoted the apparent accumulation of trophozoites, both consistent with a blockade in the hemoglobin degradation pathway. At sub-micromolar concentrations, the inhibitor-enriched fraction reduced the infection of VERO cells by T. cruzi (CL Brener clone) trypomastigotes and interfered with intracellular differentiation and/or replication of the parasites. This study provides new scientific evidence that confirms P. homomalla as an excellent source of tight-biding protease inhibitors for different proteases with biomedical relevance, and suggests that either the individual inhibitors or the enriched fraction itself could be valuable as antiparasitic compounds. Fil: Salas Sarduy, Emir. Universidad de la Habana. Facultad de Biología. Centro de Estudio de Proteínas; Cuba. Universidad Nacional de la Plata. Red CYTED-PROMAL. Proteómica y Quimiogenómica de Inhibidores de Proteasas de Origen Natural con Potencial Terapéutico en Malaria; Argentina Fil: Cabrera Muñoz, Aymara. Universidad de la Habana. Facultad de Biología. Centro de Estudio de Proteínas; Cuba Fil: Cauerff, Ana Albina. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico la Plata. Centro de Investigación y Desarrollo en Fermentaciones Industriales (i); Argentina Fil: González González, Yamile . Universidad de la Habana. Facultad de Biología. Centro de Estudio de Proteínas; Cuba. Universidad Nacional de la Plata. Red CYTED-PROMAL. Proteómica y Quimiogenómica de Inhibidores de Proteasas de Origen Natural con Potencial Terapéutico en Malaria; Argentina Fil: Trejo, Sebastian Alejandro. Universitat Autònoma de Barcelona. Servei de Proteomica i Biologia Estructural; España. Universidad Nacional de la Plata. Red CYTED-PROMAL. Proteómica y Quimiogenómica de Inhibidores de Proteasas de Origen Natural con Potencial Terapéutico en Malaria; Argentina Fil: Chidichimo, Agustina. Instituto de Investigaciones Biotecnológicas - Instituto Tecnológico Chascomús (San Martin); Argentina Fil: Chávez Planes, Maria de Los Angeles. Universidad de la Habana. Facultad de Biología. Centro de Estudio de Proteínas; Cuba. Universidad Nacional de la Plata. Red CYTED-PROMAL. Proteómica y Quimiogenómica de Inhibidores de Proteasas de Origen Natural con Potencial Terapéutico en Malaria; Argentina Fil: Cazzulo, Juan Jose. Instituto de Investigaciones Biotecnológicas - Instituto Tecnológico Chascomús (san Martin); Argentina. Universidad Nacional de la Plata. Red CYTED-PROMAL. Proteómica y Quimiogenómica de Inhibidores de Proteasas de Origen Natural con Potencial Terapéutico en Malaria; Argentina