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

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.

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

Tipo

Artigo

Data de publicação

2016

Periódico

Parasitology International

Citações (Scopus)

30

Autores

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.

Resumo

© 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