Antitumor phthalanilides active in acute and chronic Trypanosoma brucei brucei murine infections.
A series of phthalanilides and related compounds were tested on a short-term, fulminating, mouse infection of Trypanosoma brucei brucei (EATRO 110 isolate). The most effective compound was [4,4'-bis (4-methylimidazolin-2-yl)-terephthalanilide] which had a cure rate of 75% at 0.1 mg/kg body weight and 100% at 0.5 mg/kg when administered as three single daily intraperitoneal injections starting 24 hours post-infection. Several related phthalanilides and similarly substituted ureas showed definite but lower activity. In tests with a chronic neurotropic T. b. brucei isolate (TREU 667), cure rates greater than 90% were obtained with 10 or 25 mg/kg [4,4'-bis(4-methylimidazolin-2-yl)-terephthalanilide]. Cured animals survived for at least 200 days after infection with no evidence of recrudescence of parasitemia or of toxicity; blood or brain homogenates of cured animals were non-infective to immunosuppressed animals. These studies indicate that this series of compounds, previously studied as antitumor agents, should be re-examined as potential trypanocides.
D000813:Anilides / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002493:Central Nervous System Diseases / Q000188:drug therapy / Q000469:parasitology; D007093:Imidazoles / Q000627:therapeutic use; D051379:Mice; D010795:Phthalic Acids / Q000627:therapeutic use*; D014353:Trypanosomiasis, African / Q000188:drug therapy* / Q000469:parasitology
D000813:Anilides; D000970:Antineoplastic Agents; D007093:Imidazoles; D010795:Phthalic Acids; C043002:BW 458C