Ro 15-0216: a nitroimidazole compound active in vitro against human and animal pathogenic African trypanosomes.

In vitro systems for the continuous cultivation of Trypanosoma brucei brucei, T. b. gambiense, T. b. rhodesiense, T. congolense and T. vivax were used to determine the antitrypanosomal activity of the 2-substituted nitroimidazole Ro 15-0216. For all trypanosome species, the concentration which inhibited parasite growth by 50% (IC50 value) was established: 0.0957 microgram ml-1 (T. b. brucei TC221), 0.1327 microgram ml-1 (T. b. gambiense STIB 754-A), 0.0450 microgram ml-1 (T. b. rhodesiense STIB 704-BABA), 0.0896 microgram ml-1 (T. congolense ILNat 3.1) and 0.0109 microgram ml-1 (T. vivax ILRAD 1392). The IC50 value of its major metabolite Ro 19-9638 was 0.0341 microgram ml-1 (T. b. rhodesiense STIB 704-BABA). Furthermore, minimum exposure times required to render T. b. brucei non-infective for mice as well as preventing their growth in vitro have been established to be three, four, six and ten hours at drug concentrations of 30, 10, 3 and 1 microgram ml-1, respectively.