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 Ki values of 3.6 µM and 8.5 µM 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.