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.
Department of Zoology, University of Ilorin, Ilorin, Nigeria.
Awotunde J
AJ
Oluwafemi
Emmanuel O
EO
Okanla
Pelayo
P
Camps
Diego
D
Muñoz-Torrerob
Zachary B
ZB
Mackey
Peter K
PK
Chiang
Scott
S
Seville
Colin W
CW
Wright
D000818:Animals; D031106:Cryptolepis / Q000737:chemistry; D004333:Drug Administration Routes; D006801:Humans; D032501:Huperzia / Q000737:chemistry; D026121:Indole Alkaloids / Q000737:chemistry* / Q000494:pharmacology*; D015394:Molecular Structure; D011804:Quinolines / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats; D012717:Sesquiterpenes / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology*; D014344:Trypanocidal Agents / Q000737:chemistry* / Q000494:pharmacology*; D014353:Trypanosomiasis, African / Q000188:drug therapy
D026121:Indole Alkaloids; D011804:Quinolines; D012717:Sesquiterpenes; D014344:Trypanocidal Agents; C024015:cryptolepine