Evaluation of cryptolepine and huperzine derivatives as lead compounds towards new agents for the treatment of human African trypanosomiasis.

: The alkaloid cryptolepine (1) and eight synthetic analogues (2-8) were assessed for in vitro activities against Trypanosoma brucei. Four of the analogues were found to be highly potent with IC50 values of less than 3 nM and three of these were assessed against T. brucei brucei infection in rats. The most effective compound was 2, 7-dibromocryptolepine (7); a single oral dose of 20 mg/kg suppressed parasitaemia and increased the mean survival time to 13.6 days compared with 8.4 days for untreated controls. In addition, four huperzine derivatives (9-12) were shown to have in vitro antitrypanosomal activities with IC50 values ranging from 303-377 nM.