Oluwafemi A.J., Okanla E.O., Camps P., Muñoz-Torrero D., Mackey Z.B., Chiang P.K., Seville S., Wright C.W.
Department of Zoology, University of Ilorin, Ilorin, Nigeria; Laboratori de Química Farmacèutica (Unitat Associada al CSIC), Facultat de Farmàcia and Institut de Biomedicina (IBUB), University of Barcelona, Av. Diagonal 643, 08028-Barcelona, Spain; Depart
Oluwafemi, A.J., Department of Zoology, University of Ilorin, Ilorin, Nigeria; Okanla, E.O., Department of Zoology, University of Ilorin, Ilorin, Nigeria; Camps, P., Laboratori de Química Farmacèutica (Unitat Associada al CSIC), Facultat de Farmàcia and Institut de Biomedicina (IBUB), University of Barcelona, Av. Diagonal 643, 08028-Barcelona, Spain; Muñoz-Torrero, D., Laboratori de Química Farmacèutica (Unitat Associada al CSIC), Facultat de Farmàcia and Institut de Biomedicina (IBUB), University of Barcelona, Av. Diagonal 643, 08028-Barcelona, Spain; Mackey, Z.B., Department of Pathology, Sandler Centre for Basic Research in Parasitic Diseases, University of California, QB3 1700 4th St, San Francisco, CA 94158, United States; Chiang, P.K., Pharmadyn Inc., 525 Del Rey, Sunnyvale, CA 94085, United States; Seville, S., Bradford School of Pharmacy, University of Bradford, West Yorkshire, BD7 1DP, United Kingdom; Wright, C.W., Bradford School of Pharmacy, University of Bradford, West Yorkshire, BD7 1DP, United Kingdom
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.
11 chlorocryptolepine; 2 chlorocryptolepine; 2 fluorocryptolepine; 2,7 dibromocryptolepine; 7 bromocryptolepine; 7 bromocryptolepine hydrochloride; 8 chlorocryptolepine; cryptolepine; cryptolepine derivative; huperzine A; thiomersal; unclassified drug; antitrypanosomal agent; indole alkaloid; quinoline derivative; sesquiterpene; African trypanosomiasis; animal cell; animal experiment; animal model; antiprotozoal activity; article; clinical evaluation; controlled study; drug structure; female; IC 50; in vitro study; in vivo study; male; mouse; nonhuman; parasitemia; rat; reference value; single drug dose; survival time; Trypanosoma brucei; animal; chemical structure; chemistry; Cryptolepis; drug administration route; human; Huperzia; Cryptolepis sanguinolenta; Huperzia serrata; Rattus; Trypanosoma brucei; Animals; Cryptolepis; Drug Administration Routes; Humans; Huperzia; Indole Alkaloids; Molecular Structure; Quinolines; Rats; Sesquiterpenes; Trypanocidal Agents; Trypanosomiasis, African