title: Toxicity of betulin derivatives and in vitro effect on promastigotes and amastigotes of Leishmania infantum and L. donovani.
abstract: The toxicity and antileishmanial activity of 20 betulin derivatives were studied. The toxicity of betulin and synthesized compounds was determined using a bacterial test (Microtox) and two mammalian cell lines (CHO-K1 and J774). The antileishmanial activity of compounds (50  μM) was examined in both the promastigote and intracellular amastigote stages of Leishmania infantum and L. donovani. No correlation was found among the toxicity tests. All the compounds showed significant antipromastigote activity. The antiproliferative capacity of derivatives was dependent on the parasite stage studied, and no substantial differences were found between Leishmania species. Betulin, 3,28-di-O-acetylbetulin and L-aspartyl amide of betulonic acid showed moderate activity against amastigotes. The highest inhibition of intracellular amastigote multiplication was achieved with a low micromolar concentration (IC(50) ca 9  μM) of heterocyclic betulin derivative 3,28-di-O-acetyllup-13(18)-ene with N-ethyltriazolo moiety 16, without significant toxicity for mammalian cells. These results point to the interest of this lead compound for further in vitro and in vivo tests.
authors.affiliation: Department of Animal Health, Faculty of Veterinary Medicine, Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: León
authors.initials: L
authors.lastname: Wert
authors.forename: Sami
authors.initials: S
authors.lastname: Alakurtti
authors.forename: María Jesús
authors.initials: MJ
authors.lastname: Corral
authors.forename: Sebastián
authors.initials: S
authors.lastname: Sánchez-Fortún
authors.forename: Jari
authors.initials: J
authors.lastname: Yli-Kauhaluoma
authors.forename: José María
authors.initials: JM
authors.lastname: Alunda
mesh_terms: D000818:Animals; D016466:CHO Cells; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D020128:Inhibitory Concentration 50; D007893:Leishmania donovani / Q000187:drug effects*; D018314:Leishmania infantum / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects / Q000469:parasitology; D051379:Mice; D013329:Structure-Activity Relationship; D018675:Toxicity Tests; D014315:Triterpenes / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D014344:Trypanocidal Agents / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D000094062:Betulinic Acid
chemical_list: D014315:Triterpenes; D014344:Trypanocidal Agents; C002503:betulin; D000094062:Betulinic Acid