Antileishmanial activity of sodium stibogluconate fractions.
Sodium stibogluconate, a pentavalent antimony derivative produced by the reaction of stibonic and gluconic acids, is the drug of choice for the treatment of leishmaniasis. It has been reported to be a complex mixture rather than a single compound. We separated sodium stibogluconate into 12 fractions by anion-exchange chromatography. One fraction accounted for virtually all the leishmanicidal activity of the fractionated material against Leishmania panamensis promastigotes, with a 50% inhibitory concentration (IC50) of 12 micrograms of Sb per ml; that of unfractionated sodium stibogluconate was 154 micrograms of Sb per ml. Further analysis of this active fraction revealed that a major component was m-chlorocresol, which had been included in the sodium stibogluconate formulation as a preservative. The IC50 of pure m-chlorocresol was 1.6 micrograms/ml, a concentration equivalent to that present in unfractionated sodium stibogluconate at a concentration of 160 micrograms of Sb per ml. After ether extraction to remove m-chlorocresol, the IC50 of sodium stibogluconate was > 4,000 micrograms of Sb per ml. In contrast, when L. panamensis amastigotes were grown in macrophages, the IC50 of ether-extracted sodium stibogluconate was 10.3 micrograms of Sb per ml. The 12 fractions of ether-extracted sodium stibogluconate obtained by anion-exchange chromatography had IC50s of 10.1 to 15.4 micrograms of Sb per ml. We conclude that preservative-free sodium stibogluconate has little activity against L. panamensis promastigotes but is highly active against L. panamensis amastigotes in macrophages. This activity is associated with multiple chemical species.
Roberts
W L
WL
Department of Laboratory Medicine, Yale University, New Haven, Connecticut 06510.
Rainey
P M
PM
D000818:Animals; D000967:Antimony Sodium Gluconate / Q000737:chemistry / Q000494:pharmacology*; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D002460:Cell Line; D002852:Chromatography, Ion Exchange; D003408:Cresols / Q000494:pharmacology; D007891:Leishmania / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000382:microbiology; D051379:Mice; D008826:Microbial Sensitivity Tests; D013056:Spectrophotometry, Ultraviolet; D014498:Uracil / Q000378:metabolism
D000981:Antiprotozoal Agents; D003408:Cresols; C006984:chlorocresol; D014498:Uracil; D000967:Antimony Sodium Gluconate