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The cholesterol pathway of Trypanosoma congolense could be a target for triphenyltinsalicylate and triphenylsiliconsalicylate inhibition
Author(s) -
Nok Andrew J.,
Nock Ishaya H.,
Bonire Josiah J.
Publication year - 2003
Publication title -
applied organometallic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.53
H-Index - 71
eISSN - 1099-0739
pISSN - 0268-2605
DOI - 10.1002/aoc.368
Subject(s) - chemistry , in vivo , trypanosoma , in vitro , population , incubation , mode of action , lysis , toxicology , biochemistry , biology , virology , microbiology and biotechnology , demography , sociology
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.