Oleanolic acid (OA) as an antileishmanial agent: Biological evaluation and in silico mechanistic insights

Data de publicação
Parasitology International
Citações (Scopus)
Melo T.S.
Gattass C.R.
Soares D.C.
Cunha M.R.
Ferreira C.
Tavares M.T.
Saraiva E.
Parise-Filho R.
Braden H.
Delorenzi J.C.
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© 2016 Elsevier Ireland Ltd.Although a worldwide health problem, leishmaniasis is considered a highly neglected disease, lacking efficient and low toxic treatment. The efforts for new drug development are based on alternatives such as new uses for well-known drugs, in silico and synthetic studies and naturally derived compounds. Oleanolic acid (OA) is a pentacyclic triterpenoid widely distributed throughout the Plantae kingdom that displays several pharmacological activities. OA showed potent leishmancidal effects in different Leishmania species, both against promastigotes (IC50 L. braziliensis 30.47±6.35μM; IC50 L. amazonensis 40.46±14.21μM; IC50 L. infantum 65.93±15.12μM) and amastigotes (IC50 L. braziliensis 68.75±16.55μM; IC50 L. amazonensis 38.45±12.05μM; IC50 L. infantum 64.08±23.52μM), with low cytotoxicity against mouse peritoneal macrophages (CC50 235.80±36.95μM). Moreover, in silico studies performed to evaluate OA molecular properties and to elucidate the possible mechanism of action over the Leishmania enzyme sterol 14α-demethylase (CYP51) suggested that OA interacts efficiently with CYP51 and could inhibit the ergosterol synthesis pathway. Collectively, these data indicate that OA is a good candidate as leading compound for the development of a new leishmaniasis treatment.
Assuntos Scopus
Animals , Antiprotozoal Agents , Female , Humans , Leishmania , Leishmaniasis , Macrophages, Peritoneal , Male , Mice , Models, Molecular , Models, Structural , Oleanolic Acid
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