Detalle Publicación

Library of seleno-compounds as novel agents against Leishmania species
Autores: Martín-Montes, A.; Plano Amatriain, Daniel; Martín-Escolano, R.; Alcolea Devesa, Verónica; Díaz Hernando, Marta; Pérez Silanes, Silvia; Espuelas Millán, María Socorro; Moreno Amatria, Esther; Marín, C.; Gutiérrez-Sánchez, R.; Sanmartín Grijalba, Carmen; Sánchez-Moreno, M.
ISSN: 0066-4804
Volumen: 61
Número: 6
Páginas: e02546-16
Fecha de publicación: 2017
The in vitro leishmanicidal activities of a series of 48 recently synthesized selenium derivatives against Leishmania infantum and Leishmania braziliensis parasites were tested using promastigotes and intracellular amastigote forms. The cytotoxicity of the tested compounds for J774.2 macrophage cells was also measured in order to establish their selectivity. Six of the tested compounds (compounds 8, 10, 11, 15, 45, and 48) showed selectivity indexes higher than those of the reference drug, meglumine antimonate (Glucantime), for both Leishmania species; in the case of L. braziliensis, compound 20 was also remarkably selective. Moreover, data on infection rates and amastigote numbers per macrophage showed that compounds 8, 10, 11, 15, 45, and 48 were the most active against both Leishmania species studied. The observed changes in the excretion product profile of parasites treated with these six compounds were also consistent with substantial cytoplasmic alterations. On the other hand, the most active compounds were potent inhibitors of Fe superoxide dismutase (Fe-SOD) in the two parasite species considered, whereas their impact on human CuZn-SOD was low. The high activity, low toxicity, stability, low cost of the starting materials, and straightforward synthesis make these compounds appropriate molecules for the development of affordable antileishmanicidal agents.