Library of Seleno-Compounds as Novel Agents against Leishmania Species.
Thein vitroleishmanicidal activities of a series of 48 recently synthesized selenium derivatives againstLeishmania infantumandLeishmania braziliensisparasites 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 bothLeishmaniaspecies; in the case ofL. 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 bothLeishmaniaspecies 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.
Universidad de Granada, Departamento de Parasitología, Facultad de Ciencias, Severo Ochoa s/n, Granada, Spain, and Instituto de Investigación Biosanitaria (ibs. Granada), Hospitales Universitarios de Granada, Granada, Spain.
Álvaro
Á
Martín-Montes
University of Navarra, Faculty of Pharmacy and Nutrition, Departament of Organic and Pharmaceutical Chemistry, Campus Universitario, Pamplona, Spain.|IdiSNA, Instituto de Investigación Sanitaria de Navarra, Pamplona, Spain.
Daniel
D
Plano
Universidad de Granada, Departamento de Parasitología, Facultad de Ciencias, Severo Ochoa s/n, Granada, Spain, and Instituto de Investigación Biosanitaria (ibs. Granada), Hospitales Universitarios de Granada, Granada, Spain.
Rubén
R
Martín-Escolano
University of Navarra, Faculty of Pharmacy and Nutrition, Departament of Organic and Pharmaceutical Chemistry, Campus Universitario, Pamplona, Spain.|IdiSNA, Instituto de Investigación Sanitaria de Navarra, Pamplona, Spain.
Verónica
V
Alcolea
University of Navarra, Faculty of Pharmacy and Nutrition, Departament of Organic and Pharmaceutical Chemistry, Campus Universitario, Pamplona, Spain.|IdiSNA, Instituto de Investigación Sanitaria de Navarra, Pamplona, Spain.
Marta
M
Díaz
University of Navarra, Faculty of Pharmacy and Nutrition, Departament of Organic and Pharmaceutical Chemistry, Campus Universitario, Pamplona, Spain.|Institute of Tropical Health, University of Navarra, Pamplona, Spain.
Silvia
S
Pérez-Silanes
Institute of Tropical Health, University of Navarra, Pamplona, Spain.
Socorro
S
Espuelas
Institute of Tropical Health, University of Navarra, Pamplona, Spain.
Esther
E
Moreno
Universidad de Granada, Departamento de Parasitología, Facultad de Ciencias, Severo Ochoa s/n, Granada, Spain, and Instituto de Investigación Biosanitaria (ibs. Granada), Hospitales Universitarios de Granada, Granada, Spain.
Clotilde
C
Marín
Department of Statistics, University of Granada, Severo Ochoa s/n, Granada, Spain.
Ramón
R
Gutiérrez-Sánchez
University of Navarra, Faculty of Pharmacy and Nutrition, Departament of Organic and Pharmaceutical Chemistry, Campus Universitario, Pamplona, Spain sanmartin@unav.es msanchem@ugr.es.|IdiSNA, Instituto de Investigación Sanitaria de Navarra, Pamplona, Spain.
Carmen
C
Sanmartín
Universidad de Granada, Departamento de Parasitología, Facultad de Ciencias, Severo Ochoa s/n, Granada, Spain, and Instituto de Investigación Biosanitaria (ibs. Granada), Hospitales Universitarios de Granada, Granada, Spain sanmartin@unav.es msanchem@ugr.es.
Manuel
M
Sánchez-Moreno
D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D006801:Humans; D007892:Leishmania braziliensis / Q000187:drug effects* / Q000378:metabolism; D018314:Leishmania infantum / Q000187:drug effects* / Q000378:metabolism; D008536:Meglumine / Q000494:pharmacology*; D000077485:Meglumine Antimoniate; D009942:Organometallic Compounds / Q000494:pharmacology*; D021261:Parasitic Sensitivity Tests; D012643:Selenium / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
D000981:Antiprotozoal Agents; D009942:Organometallic Compounds; D008536:Meglumine; D000077485:Meglumine Antimoniate; D013482:Superoxide Dismutase; D012643:Selenium
Leishmania; glucose metabolism; selenium; superoxide dismutase