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 par...

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Bibliographic Details
Published in:Biochemical journal 1993, Vol.289 (1), p.155-160
Main Authors: CANTOS, G, BARBIERI, C. L, IACOMINI, M, GORIN, P. A. J, TRAVASSOS, L. R
Format: Article
Language:English
Subjects:
Animals
Antibiotics. Antiinfectious agents. Antiparasitic agents
Antimony - chemistry
Antimony - pharmacokinetics
Antimony - pharmacology
Antiparasitic agents
Antiprotozoal Agents - chemistry
Antiprotozoal Agents - pharmacokinetics
Antiprotozoal Agents - pharmacology
Biological and medical sciences
Carbohydrate Sequence
Cricetinae
Drug Carriers
Lectins, C-Type
Leishmania - drug effects
Leishmaniasis - drug therapy
Macrophages - metabolism
Macrophages - parasitology
Mannans - chemistry
Mannose - pharmacology
Mannose-Binding Lectins
Medical sciences
Meglumine - pharmacology
Meglumine Antimoniate
Mice
Molecular Sequence Data
Organometallic Compounds - pharmacology
Pharmacology. Drug treatments
Receptors, Cell Surface
Receptors, Immunologic - metabolism
Saccharomyces cerevisiae - chemistry
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Summary: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.
ISSN:0264-6021
1470-8728
DOI:10.1042/bj2890155