Synthesis and preliminary evaluation of new ursolic and oleanolic acids derivatives as antileishmanial agents

Abstract

A series of new ursolic and oleanolic acids derivatives was synthesized via ursolic or oleanolic acids, previously extracted from South American Ilex species. These new compounds were tested for in vitro antiparasitic activity on Leishmania amazonensis and Leishmania infantum strains. Some of these compounds showed activity against the promastigote forms of L. amazonensis or L. infantum, with IC 50 ranging from 5 to 12 mM. As expected, most of the compounds showed a significant level of cytotoxicity against monocytes (IC 50 ¼ 2-50 mM). From a structure-activity relationships point of view, these pharmacological results enlightened mainly the importance of an acetylation at position 3 of the oleanolic acid skeleton in the activity against the L. amazonensis strain, and of a bis-(3-aminopropyl)piperazine moiety on the carboxylic function of ursolic acid against the L. infantum strain.

Anti-leishmanial effects of purified compounds from aerial parts of Baccharis uncinella C. DC. (Asteraceae)

“…Studies conducted by Tan et al (2002) demonstrated that oleanolic and ursolic acids from Salvia cilica were more efficient in the elimination of intracellular forms of Leishmania donovani and Leishmania major than promastigotes, indicating that amastigotes present elevated sensibility to these compounds. In addition, other studies have demonstrated the potential of synthesized oleanolic and ursolic acids in the elimination of L (L.) amazonensis and L. donovani parasites (Gnoatto et al 2008), indicating the possibility of large-scale production of both compounds; moreover, the strong inhibitory activity against different species of Leishmania reinforcing the possibility of drug development. Besides oleanolic+ursolic acids and pectolinaringenin, caffeic acid also presented moderate activity against amastigote forms of L. (L.) amazonensis, but weak against L. (V.) braziliensis amastigotes, and low cytotoxicity has been verified on J774 macrophages.…”

In vitro antitrypanosomal and antileishmanial activity of plants used in Benin in traditional medicine and bio-guided fractionation of the most active extract

“…Antileishmanial activity of ursolic acid was also evaluated against promastigotes of Leishmania amazonensis (IC 50 = 43.8 and 5 g/ml, depending on the test) (Torres-Santos et al, Gnoatto et al, 2008) and against promastigotes of Leishmania donovani (IC 50 = 3.5 g/ml) (Moulisha et al, 2010). The activity of oleanolic acid against promastigotes of Leishmania amazonensis gave an IC 50 of 10 g/ml (Torres-Santos et al, 2004).…”

Antiparasitic compounds from Cornus florida L. with activities against Plasmodium falciparum and Leishmania tarentolae

“…In previous studies it was shown that ursolic acid (2) had moderate activity against L. amazonensis but was inactive against L. infantum (Gnoatto et al, 2008). Also, Torres-Santos et al showed that ursolic acid isolated from Pourouma guianensis Aublet (Moraceae) had a mild in vitro activity (IC 50 ¼59 mM) against intracellular amastigotes of Leishmania amazonensis (Torres-Santos et al, 2004).…”