title: Oleanolic acid (OA) as an antileishmanial agent: Biological evaluation and in silico mechanistic insights.
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.
authors.affiliation: Centro de Ciências Biológicas e da Saúde, Universidade Presbiteriana Mackenzie, São Paulo, Brazil.
authors.forename: Tahira Souza
authors.initials: TS
authors.lastname: Melo
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Cerli Rocha
authors.initials: CR
authors.lastname: Gattass
authors.affiliation: Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Deivid Costa
authors.initials: DC
authors.lastname: Soares
authors.affiliation: Centro de Ciências Biológicas e da Saúde, Universidade Presbiteriana Mackenzie, São Paulo, Brazil; Laboratório de Planejamento e Síntese de Substâncias Bioativas (LAPESSB), Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Micael Rodrigues
authors.initials: MR
authors.lastname: Cunha
authors.affiliation: Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Christian
authors.initials: C
authors.lastname: Ferreira
authors.affiliation: Laboratório de Planejamento e Síntese de Substâncias Bioativas (LAPESSB), Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Maurício Temotheo
authors.initials: MT
authors.lastname: Tavares
authors.affiliation: Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Elvira
authors.initials: E
authors.lastname: Saraiva
authors.affiliation: Laboratório de Planejamento e Síntese de Substâncias Bioativas (LAPESSB), Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Roberto
authors.initials: R
authors.lastname: Parise-Filho
authors.affiliation: Centro de Ciências Biológicas e da Saúde, Universidade Presbiteriana Mackenzie, São Paulo, Brazil; Wright State University, Dayton, OH, United States of America.
authors.forename: Hannah
authors.initials: H
authors.lastname: Braden
authors.affiliation: Centro de Ciências Biológicas e da Saúde, Universidade Presbiteriana Mackenzie, São Paulo, Brazil. Electronic address: jan.bertassoni@mackenzie.br.
authors.forename: Jan Carlo
authors.initials: JC
authors.lastname: Delorenzi
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007891:Leishmania / Q000187:drug effects*; D007896:Leishmaniasis / Q000188:drug therapy* / Q000469:parasitology; D017737:Macrophages, Peritoneal / Q000469:parasitology; D008297:Male; D051379:Mice; D008958:Models, Molecular; D008961:Models, Structural; D009828:Oleanolic Acid / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000981:Antiprotozoal Agents; D009828:Oleanolic Acid
keywords: CYP51; In silico studies; Leishmania spp.; Leishmaniasis; Oleanolic acid