A study of the trypanocidal activity of triterpene acids isolated from Miconia species.
Triterpene acids, including ursolic acid (1), urjinolic acid (4) and oleanoic acid (5) along with a mixture of 2alpha-hydroxyursolic acid (2) and maslic acid (3) were isolated from methylene chloride extracts of the Miconia sellowiana and M. ligustroides species and their activities against the trypomastigote blood forms of Trypanosoma cruzi were evaluated. The potassium salt derivative of ursolic acid (1a) was also tested. The in vitro assays showed that compounds 1, 5 and 1a were the most active (IC(50) 17.1 microm, 12.8 microm and 8.9 microm, respectively). In contrast, a mixture of 2 plus 3, that exhibit a hydroxyl at C-2 and C-3, is much less potent than a mixture of 1 and 5 (IC(50) 48.5 microm and 11.8 microm, respectively). In the same manner, compound 4, that differs from 5 by two additional hydroxyl groups (at C-2 and C-23) displayed weak trypanocidal activity (IC(50) 76.3 microm) when compared with the other triterpenes. These results suggest that the free hydroxyl at C-3 and the polarity of C-28 are the most influential structural features for determining the in vitro trypanocidal activity of triterpenes. In vivo assays were also undertaken for the most active compounds 1, 1a and the mixture of 1 plus 5. The most significant reduction in parasite number in the parasitemic peak were obtained for compound 1 and its salt derivative 1a (75.7% and 70.4%, respectively). Moreover, the survival time was increased for all the treated animals.
Cunha
Wilson Roberto
WR
Núcleo de Pesquisas em Ciências Exatas e Tecnológicas da Universidade de Franca, Franca, SP, Brasil. wrcunha@unifran.br
Crevelin
Eduardo J
EJ
Arantes
Glenda M
GM
Crotti
Antonio E Miller
AE
Andrade e Silva
Márcio L
ML
Furtado
Niege A J Cardoso
NA
Albuquerque
Sérgio
S
Ferreira
Daniele Da Silva
Dda S
D000818:Animals; D035322:Melastomataceae / Q000737:chemistry*; D051379:Mice; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014315:Triterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D014344:Trypanocidal Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D014349:Trypanosoma cruzi / Q000187:drug effects
D014315:Triterpenes; D014344:Trypanocidal Agents