title: Selective antileishmania activity of 13,28-epoxy-oleanane and related triterpene saponins from the plant families Myrsinaceae, Primulaceae, Aceraceae and Icacinaceae.
abstract: Maesa saponins with the 13,28-epoxy-oleanane triterpene core skeleton were described recently to possess strong and selective in vitro and in vivo antileishmania activity. In the absence of direct chemical derivatization possibilities, a structure-based literature search was carried out to explore a structure-activity relationship. Crude alcohol extracts from several plant species of Myrsinaceae, Primulaceae, Aceraceae and Icacinaceae were evaluated for in vitro activity against Leishmania infantum intracellular amastigotes and cytotoxicity on MRC-5(SV2) cells, while the saponin content was evaluated qualitatively by TLC. A clear correlation was found between the presence of close analogue 13,28-epoxy-oleanane triterpene saponins and potent and selective antileishmania activity. This was most striking in Maesa species, except for M. macrosepala. Interesting activities were also found in extracts that did not exactly match the TLC characteristics of the Maesa saponin references, as was the case for Ardisia angusta, A. amherstiana, A. caudata, A. gigantifolia, A. roseiflora, Myrsine affinis, Acer brevipes and A. laurinum var. petelotii. This study indicates that the 13,28-epoxy-oleanane triterpene moiety is essential for selective antileishmania potential and that several other plant species could still be explored for antileishmania drug discovery.
authors.affiliation: Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, Antwerp University, Antwerp, Belgium.
authors.forename: Marieke
authors.initials: M
authors.lastname: Vermeersch
authors.forename: Kenn
authors.initials: K
authors.lastname: Foubert
authors.forename: Raquel Inocêncio
authors.initials: RI
authors.lastname: da Luz
authors.forename: Luc
authors.initials: L
authors.lastname: Van Puyvelde
authors.forename: Luc
authors.initials: L
authors.lastname: Pieters
authors.forename: Paul
authors.initials: P
authors.lastname: Cos
authors.forename: Louis
authors.initials: L
authors.lastname: Maes
mesh_terms: D000818:Animals; D000977:Antiparasitic Agents / Q000032:analysis / Q000494:pharmacology*; D002460:Cell Line; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D018314:Leishmania infantum / Q000187:drug effects*; D008264:Macrophages / Q000469:parasitology; D019684:Magnoliopsida / Q000737:chemistry*; D051379:Mice; D008815:Mice, Inbred Strains; D008826:Microbial Sensitivity Tests; D009828:Oleanolic Acid / Q000032:analysis / Q000737:chemistry / Q000494:pharmacology*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D029623:Primulaceae / Q000737:chemistry*; D012503:Saponins / Q000032:analysis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000977:Antiparasitic Agents; D010936:Plant Extracts; D012503:Saponins; D009828:Oleanolic Acid