The cholesterol pathway of Trypanosoma congolense could be a target for triphenyltinsalicylate and triphenylsiliconsalicylate inhibition

The organometallic compounds triphenyltinsalicylate (TPTS) and triphenylsiliconsalicylate (TPSS) were found to be trypanocidal against culture forms of Trypanosoma congolense . Both compounds at 0.4–5 µmol ml −1 completely killed the parasites in vitro within 3‐8 min after incubation. A dosage of 1.5 µmol ml −1 TPTS killed at least 50% of the parasite population, which was preceded by a cluster effect as observed under phase contrast microscopy. Also, 3.5 µg ml −1 of TPSS was required to kill 50% of the T. congolense cells. At a low dosage of 2–10 µg ml −1 , it was feasible to monitor the effect and mode of action of the organometallic compounds. There was a 50% reduction in the amount of synthesized cholesterols in the presence of 6 µg ml −1 and 10 µg ml −1 of TPTS and TPSS respectively. TPTS and TPSS also non‐competitively inhibited pyrophosphatase from lysed T. congolense with K i values of 3.6 µ M and 8.5 µ M respectively. In the in vivo experiments, TPTS cured T. congolense infected mice at a dosage of 2–10 mg kg day −1 for 4 days. TPSS was, however, completely inactive in vivo . The use of organometallic compounds in the design of trypanocides is discussed. Copyright © 2002 John Wiley & Sons, Ltd.