Leishmanicidal effect of LLD-3 (1), a nor-triterpene isolated from Lophanthera lactescens.
Leishmanicidal activity of 6alpha, 7alpha, 15beta, 16beta, 24-pentacetoxy-22alpha-carbometoxy-21beta,22beta-epoxy-18beta-hydroxy-27,30-bisnor-3,4-secofriedela-1,20 (29)-dien-3,4 R-olide (LLD-3 (1)) isolated from Lophanthera lactescens Ducke, a member of the Malpighiaceae, was demonstrated against intramacrophage amastigote forms (IC(50) of 0.41mug/mL). The in vitro leishmanicidal effect of Glucantime, the first choice drug for leishmaniasis treatment, was increased by LLD-3 (1) association. The leishmanicidal effect of LLD-3 (1) was not due to stimulation of nitric oxide production by macrophages. LLD-3 (1) was also not cytotoxic for mouse peritoneal macrophages or B cells as assessed by the XTT and Trypan blue exclusion assays. LLD-3 (1) was unable to affect proliferation of naïve or activated B and T cells, as well as the B cells immunoglobulin synthesis. Cellularity of different tissues, liver and kidney functions were not altered in mice treated with LLD-3 (1), as well as the histology pattern of different organs. Our results add LLD-3 (1) as a potential drug candidate for treatment of leishmaniasis.
Danelli
M G M
MG
Departamento de Microbiologia e Imunologia Veterinária, Universidade Federal Rural do Rio de Janeiro, RJ 23890-000, Brazil.
Soares
D C
DC
Abreu
H S
HS
Peçanha
L M T
LM
Saraiva
E M
EM
D000818:Animals; D000981:Antiprotozoal Agents / Q000302:isolation & purification / Q000494:pharmacology*; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects; D049109:Cell Proliferation; D005260:Female; D066298:In Vitro Techniques; D007891:Leishmania / Q000187:drug effects*; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000187:drug effects; D029581:Malpighiaceae / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D014315:Triterpenes / Q000302:isolation & purification / Q000494:pharmacology*
D000981:Antiprotozoal Agents; C541865:LLD-3 compound; D014315:Triterpenes