Synthesis of antimony complexes of yeast mannan and mannan derivatives and their effect on Leishmania-infected macrophages

Biochem J. 1993 Jan 1;289 ( Pt 1)(Pt 1):155-60. doi: 10.1042/bj2890155.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antimony / chemistry
  • Antimony / pharmacokinetics
  • Antimony / pharmacology*
  • Antiprotozoal Agents / chemistry
  • Antiprotozoal Agents / pharmacokinetics
  • Antiprotozoal Agents / pharmacology*
  • Carbohydrate Sequence
  • Cricetinae
  • Drug Carriers
  • Lectins, C-Type*
  • Leishmania / drug effects*
  • Leishmaniasis / drug therapy
  • Macrophages / metabolism
  • Macrophages / parasitology*
  • Mannans* / chemistry
  • Mannose / pharmacology
  • Mannose Receptor
  • Mannose-Binding Lectins*
  • Meglumine / pharmacology
  • Meglumine Antimoniate
  • Mice
  • Molecular Sequence Data
  • Organometallic Compounds / pharmacology
  • Receptors, Cell Surface*
  • Receptors, Immunologic / metabolism
  • Saccharomyces cerevisiae / chemistry

Substances

  • Antiprotozoal Agents
  • Drug Carriers
  • Lectins, C-Type
  • Mannans
  • Mannose Receptor
  • Mannose-Binding Lectins
  • Organometallic Compounds
  • Receptors, Cell Surface
  • Receptors, Immunologic
  • Meglumine
  • Meglumine Antimoniate
  • Antimony
  • Mannose