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Antimicrobial Agents and Chemotherapy, June 2000, p. 1494-1498, Vol. 44, No. 6
Department of Infectious and Tropical
Diseases, London School of Hygiene and Tropical Medicine, London WC1E
7HT,1 and Glaxo Wellcome Research and
Development, Medicines Research Centre, Stevenage, Herts SG1
2NY,2 United Kingdom
Received 28 December 1999/Returned for modification 7 February
2000/Accepted 6 March 2000
Tucaresol, a novel immunomodulator, was inactive against
Leishmania donovani amastigotes in both peritoneal and bone
marrow macrophages in vitro at concentrations between 100 and 1 µM,
with toxicity to macrophages and parasites at 300 µM. However,
against L. donovani in BALB/c mice at doses between 80 and
1.25 mg/kg of body weight administered once daily by the oral route
during days 7 to 11 of infection, an optimal dose of 5 mg/kg produced a
43.8 to 62.4% suppression of liver amastigotes, with significantly reduced activity at the extremes of the dose range. This response was
not related to levels of infection. No interaction with the standard
pentavalent antimonial sodium stibogluconate (Pentostam) was observed
during this period of infection. The optimum dose of 5 mg/kg was
ineffective when administered during the first week of infection and
was most effective against the liver infection when administered during
weeks 2 to 3 of infection (42.3 to 46.8% inhibition) and against the
splenic infection when administered during week 6 of infection (59.5%
inhibition). The optimum dose of tucaresol against L. donovani in C57BL/6 mice was 5 mg/kg, which produced a 40.8 to
48.7% suppression of liver amastigotes when administered in a range of
80 to 1.25 mg/kg during days 7 to 11 of infection. The drug had no
activity against L. donovani infections in C.B-17
scid mice when the same regimen was used.
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Activity of the Novel Immunomodulatory Compound
Tucaresol against Experimental Visceral Leishmaniasis
*
Corresponding author. Mailing address: Department of
Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, United Kingdom. Phone: 44 (0)
20 7927 2345. Fax: 44 (0) 20 7636 8739. E-mail:
simon.croft{at}lshtm.ac.uk.
Antimicrobial Agents and Chemotherapy, June 2000, p. 1494-1498, Vol. 44, No. 6
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
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