Synthesis and preliminary evaluation of new ursolic and oleanolic acids derivatives as antileishmanial agents.
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 microM. As expected, most of the compounds showed a significant level of cytotoxicity against monocytes (IC(50) = 2-50 microM). 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.
Gnoatto
Simone C B
SC
Faculdade de Farmacia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Dalla Vechia
Luciana
L
Lencina
Claiton L
CL
Dassonville-Klimpt
Alexandra
A
Da Nascimento
Sophie
S
Mossalayi
Djavad
D
Guillon
Jean
J
Gosmann
Grace
G
Sonnet
Pascal
P
D000818:Animals; D000981:Antiprotozoal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D007891:Leishmania / Q000187:drug effects*; D018314:Leishmania infantum / Q000187:drug effects; D007894:Leishmania mexicana / Q000187:drug effects; D009000:Monocytes / Q000187:drug effects; D009828:Oleanolic Acid / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014315:Triterpenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000097245:Ursolic Acid
D000981:Antiprotozoal Agents; D009828:Oleanolic Acid; D014315:Triterpenes; D000097245:Ursolic Acid