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The trypanocidal activity of various aromatic bisguanylhydrazones in vivo
Author(s) -
Ulrich Peter C.,
Grady Robert W.,
Cerami Anthony
Publication year - 1982
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.430020211
Subject(s) - parasitemia , trypanosoma brucei , pharmacology , in vivo , clearance , drug , trypanosoma , infectivity , trypanocidal agent , active metabolite , chemistry , biology , medicine , pharmacokinetics , immunology , virology , biochemistry , malaria , plasmodium falciparum , virus , microbiology and biotechnology , gene , urology
Seven aromatic bisguanylhydrazones and two related compounds were screened against Trypanosoma brucei (EATRO 110M) in mice. The four most active were then screened against T. congolense (TREU 1183) in mice and rats. Eradication of parasitemia through 28 ( T. brucei ) or 42 days ( T. congolense ) resulting from a single dose of drug administered IP either 4 or 24 hours (respectively) after infection was used as the criterion of activity. 1,3‐Diacetylbenzene bisguanylhydrazone dihydrochloride cleared T. congolense from 50% of the animals (ED 50 ) at a dose of approximately 10 mg/kg and from mice infected with T. brucei at approximately 15 mg/kg. This drug was also active when given 5 days after infection with T. congolense (ED 50 ≅ 15 mg/kg). The isomorphous pyridine derivative, 2,6‐diacetylpyridine bisguanylhydrazone dihydrochloride, was active against T. brucei in mice (ED 50 ≅ 8 mg/kg), but noncurative against T. congolense . At therapeutic doses of these two compounds, reversal and clearance of parasitemia was often not observed for 2–4 days, suggesting a delayed mode of action. Moreover, 1–2 days after drug treatment, the infectivity of parasites obtained from treated animals was significantly reduced, if not abolished. These findings indicate that more intensive screening of aromatic bisguanylhydrazones against various species of trypanosomes is warranted.