Synthesis of antimony complexes of yeast mannan and mannan derivatives and their effect on Leishmania-infected macrophages.
Antimony(Sb)-yeast mannan complexes were synthesized as a strategy to introduce Sb into macrophages infected with Leishmania amastigotes. The complexes were taken up by endocytosis after specific recognition by alpha-D-mannosyl receptors on the macrophage membrane. About 90% of the intracellular parasites were destroyed by Sb-mannan in vitro, whereas the corresponding Sb concentration used as the pentavalent antimonial drug glucantime destroyed about 60% of the amastigotes. None of the Sb complexes prepared with mannan acid or basic derivatives was as effective as the simple Sb-mannan complex in clearing macrophage infection by Leishmania (L) amazonensis. The leishmanicidal effect of Sb-mannan was also demonstrated in vivo with infected hamsters. The alternative use of Sb-mannan complex in the treatment of human leishmaniasis is envisaged on the basis of parasite-killing efficiency and the use of a low antimony dose.
Cantos
G
G
Department of Biochemistry, Federal University of Paraná, Curitiba, PR, Brazil.
Barbieri
C L
CL
Iacomini
M
M
Gorin
P A
PA
Travassos
L R
LR
D000818:Animals; D000965:Antimony / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D000981:Antiprotozoal Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D002240:Carbohydrate Sequence; D006224:Cricetinae; D004337:Drug Carriers; D037181:Lectins, C-Type; D007891:Leishmania / Q000187:drug effects*; D007896:Leishmaniasis / Q000188:drug therapy; D008264:Macrophages / Q000378:metabolism / Q000469:parasitology*; D008351:Mannans / Q000737:chemistry; D008358:Mannose / Q000494:pharmacology; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D008536:Meglumine / Q000494:pharmacology; D000077485:Meglumine Antimoniate; D051379:Mice; D008969:Molecular Sequence Data; D009942:Organometallic Compounds / Q000494:pharmacology; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000737:chemistry
D000981:Antiprotozoal Agents; D004337:Drug Carriers; D037181:Lectins, C-Type; D008351:Mannans; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D009942:Organometallic Compounds; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D008536:Meglumine; D000077485:Meglumine Antimoniate; D000965:Antimony; D008358:Mannose