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Antimicrob Agents Chemother. 1985 June; 27(6): 916-920

Biochemical mechanisms of the antileishmanial activity of sodium stibogluconate.

J D Berman, D Waddell and B D Hanson

ABSTRACT

Pentavalent antimonial agents such as sodium stibogluconate (Pentostam; Burroughs Wellcome Co., London, United Kingdom) are the drugs of choice for the treatment of leishmaniasis, but their biochemical mechanisms of action are virtually unknown. The viability of Leishmania mexicana (WR 227) promastigotes and amastigotes was decreased 40 to 61% by a 4-h exposure to 500 micrograms of Sb (in the form of stibogluconate) per ml. Such exposure also resulted in a 51 to 65% decrease in incorporation of label into DNA, RNA, and protein; a 56 to 65% decrease in incorporation of label into purine nucleoside triphosphate; and a 34 to 60% increase in incorporation of label into purine nucleoside monophosphate and diphosphate. It is postulated that the apparent decrease in ATP and GTP synthesis from ADP and GDP contributes to decreased macromolecular synthesis and to decreased Leishmania viability. Further experiments suggested that inhibition of glycolysis and the citric acid cycle may partially explain the inability to phosphorylate ADP.

Antimicrob Agents Chemother. 1985 June; 27(6): 916-920




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