Oleanolic acid (OA) as an antileishmanial agent: Biological evaluation and in silico mechanistic insights.
Parasitol Int
; 65(3): 227-37, 2016 Jun.
Article
em En
| MEDLINE
| ID: mdl-26772973
ABSTRACT
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 (IC(50 L. braziliensis) 30.47 ± 6.35 µM; IC(50 L. amazonensis) 40.46 ± 14.21 µM; IC(50 L. infantum) 65.93 ± 15.12 µM) and amastigotes (IC(50 L. braziliensis) 68.75 ± 16.55 µM; IC(50 L. amazonensis) 38.45 ± 12.05 µM; IC(50 L. infantum) 64.08 ± 23.52 µM), with low cytotoxicity against mouse peritoneal macrophages (CC(50) 235.80 ± 36.95 µM). 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.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Ácido Oleanólico
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Leishmaniose
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Leishmania
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Antiprotozoários
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article