Synthesis and preliminary evaluation of new ursolic and oleanolic acids derivatives as antileishmanial agents |
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Authors: | Simone C B Gnoatto Luciana Dalla Vechia Claiton L Lencina Alexandra Dassonville-Klimpt Sophie Da Nascimento Djavad Mossalayi |
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Institution: | 1. Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul (UFRGS)Av. Ipiranga, 2752, Porto Alegre 90610-000, RS, Brazil;2. Laboratoire des GlucidesUMR-CNRS 6219, Faculté de Pharmacie, Université de Picardie Jules Verne, 1 Rue des Louvels, 80037 Amiens, Cedex 1, France;3. PPF Médicaments-Parasitologie, UFR des Sciences Pharmaceutiques, Université Bordeaux 2, 146 rue Léo Saignat, 33076 Bordeaux Cedex, France |
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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. |
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Keywords: | Ursolic acid oleanolic acid antileishmanial agents leishmania amazonensis leishmania infantum pentacyclic triterpene hemisynthesis |
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