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

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 +/- 6.35 mu M: IC50 L. amazonensis 40.46 +/- 14.21 mu M; IC50 L. infantum 65.93 +/- 15.12 mu M) and amastigotes (IC50 L. braziliensis 68.75 +/- 16.55 mu M; IC50 L. amazonensis 38.45 +/- 12.05 M; IC50 L. infantum 64.08 +/- 23.52 mu M), with low cytotoxicity against mouse peritoneal macrophages (CC50 235.80 +/- 36.95 mu M). Moreover, in silico studies performed to evaluate OA molecular properties and to elucidate the possible mechanism of action over the Leishmania enzyme sterol 14 alpha-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. (C) 2016 Elsevier Ireland Ltd. All rights reserved.