Author:
Berman J D,Waddell D,Hanson B D
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.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
Reference16 articles.
1. Berman J. D. 1983. Leishmaniasis p. 27-29. In H. Conn (ed.) Current therapy. The W. B. Saunders Co. Philadelphia.
2. Activity of antileishmanial agents against amastigotes in human monocyte-derived macrophages 4nd in mouse peritoneal macrophages;Berman J. D.;J. Parasitol.,1984
3. The relationship between inhibitioi of phosphofructokinase activity and the mode of action of trivalen organic antimonials on Schistosoma mansoni;Bueding E.;Br. J. Pharmacol.,1957
4. Human cutaneous Leishmania in a mouse macrophage line: propagation and isolation of intracellular parasites;Chang K. P.;Science,1980
5. Identification of Leishmania spp. by radiorespirometry;Decker J. E.;J. Protozool.,1977