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 IC₅₀ ranging from 5 to 12 μM. As expected, most of the compounds showed a significant level of cytotoxicity against monocytes (IC₅₀ = 2-50 μM). 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.

• Ursolic acid
• oleanolic acid
• antileishmanial agents
• leishmania amazonensis
• leishmania infantum
• pentacyclic triterpene
• hemisynthesis

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.