title: In vitro antileishmanial properties of tri- and pentavalent antimonial preparations.
abstract: To better understand the antileishmanial effects of antimonial agents we synthesized complexes of tri- and pentavalent antimony with mannan. The 50% inhibitory concentrations (IC50s) of these agents, along with those of potassium antimony tartrate [Sb(III)] and sodium stibogluconate [Sb(V)], were determined for promastigotes and intramacrophage amastigotes. The trivalent antimonial agents were more potent than the pentavalent agents. Although the IC50s were 60- to more-than-600-fold higher for promastigotes than for amastigotes, similar intracellular antimony concentrations in both life forms were measured after incubation with all four drugs at their respective IC50s. Macrophages accumulated antimony during a 4-h exposure that was retained intracellularly for at least 3 days. Amastigotes inside macrophages had a higher antimony content 6 days after a single 4-h treatment than they did immediately after treatment, suggesting that macrophages serve as a reservoir for antimonial agents and prolong parasite exposure. Macrophages concentrated antimony from the medium with potassium antimony tartrate, trivalent antimony-mannan, and pentavalent antimony-mannan treatments. N-Acetylcysteine antagonized the antileishmanial effects of these three drugs against intracellular amastigotes; in contrast, it had minimal effects on the action of sodium stibogluconate.
authors.affiliation: Department of Laboratory Medicine, Yale University School of Medicine, New Haven, Connecticut 06520-8035, USA.
authors.forename: W L
authors.initials: WL
authors.lastname: Roberts
authors.forename: J D
authors.initials: JD
authors.lastname: Berman
authors.forename: P M
authors.initials: PM
authors.lastname: Rainey
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D000965:Antimony / Q000032:analysis / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000966:Antimony Potassium Tartrate / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000967:Antimony Sodium Gluconate / Q000494:pharmacology; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D004338:Drug Combinations; D006801:Humans; D066298:In Vitro Techniques; D007891:Leishmania / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects; D008351:Mannans / Q000032:analysis / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010274:Parasitology / Q000379:methods
chemical_list: D000981:Antiprotozoal Agents; D004338:Drug Combinations; D008351:Mannans; D000965:Antimony; D000966:Antimony Potassium Tartrate; D000967:Antimony Sodium Gluconate; D000111:Acetylcysteine