The effect of spiroarsoranes on Trypanosoma brucei brucei and T. b. rhodesiense

Abstract

Topical application and intraperitoneal administration of spiroarsoranes were carried out to cure central nervous system (CNS) trypanosomiasis in the chronic Trypanosoma brucei GVR 35 mouse model. Topical application appeared more efficient than intraperitoneal injection. The periods of aparasitaemia after treatment were longer but none of the mice was permanently cured. Combination treatment with eflornithine (DFMO) and the spiroarsoranes failed to show any synergistic effect. In addition, spiroarsorane I was evaluated against the T. b. rhodesiense KETRI 2634 strain, whereby 60-mg/kg treatment produced a noticeable prolongation of the life span of trypanosome-positive animals. These in vivo results suggests that the spiroarsoranes have difficulty in crossing the blood-brain barrier (BBB) and clearing the parasites from the CNS or, alternatively, that these strains are less sensitive to pentavalent arsenicals than the T. b. brucei CMP fast strain, which in the present study was more sensitive to spiroarsoranes whose lipophilicity corresponded to a log-P value ranging from 2.5 to 3.7.

Metal Compounds against Neglected Tropical Diseases

“…Loiseau et al 367 investigated analogues of spiroarsorane I, testing spiroarsoranes I, II, and III (Figure 86) in murine T. brucei CNS models. Dreyfuss et al in 1988 showed that subcutaneous administration of spiroarsorane I (75 μmol/kg) was effective against both stages of the disease in infected sheep.…”

“…Loiseau et al investigated analogues of spiroarsorane I, testing spiroarsoranes I, II, and III (Figure ) in murine T. brucei CNS models.…”