title: Anthelmintic, Antibacterial and Cytotoxicity Activity of Imidazole Alkaloids from Pilocarpus microphyllus Leaves.
abstract: Pilocarpus microphyllus Stapf ex Wardlew (Rutaceae), popularly known as jaborandi, is a plant native to the northern and northeastern macroregions of Brazil. Several alkaloids from this species have been isolated. There are few reports of antibacterial and anthelmintic activities for these compounds. In this work, we report the antibacterial and anthelmintic activity of five alkaloids found in P. microphyllus leaves, namely, pilosine, epiisopilosine, isopilosine, epiisopiloturine and macaubine. Of these, only anthelmintic activity of one of the compounds has been previously reported. Nuclear magnetic resonance, HPLC and mass spectrometry were combined and used to identify and confirm the structure of the five compounds. As regards the anthelmintic activity, the alkaloids were studied using in vitro assays to evaluate survival time and damaged teguments for Schistosoma mansoni adult worms. We found epiisopilosine to have anthelmintic activity at very low concentrations (3.125 μg mL-1); at this concentration, it prevented mating, oviposition, reducing motor activity and altered the tegument of these worms. In contrast, none of the alkaloids showed antibacterial activity. Additionally, alkaloids displayed no cytotoxic effect on vero cells. The potent anthelmintic activity of epiisopilosine indicates the potential of this natural compound as an antiparasitic agent. Copyright © 2017 John Wiley & Sons, Ltd.
authors.affiliation: Programa de Mestrado em Biotecnologia (PPGBiotec), Campus de Parnaíba, Universidade Federal do Piauí (UFPI), Parnaíba, PI, Brazil.|Núcleo de Pesquisa em Biodiversidade e Biotecnologia, Biotec, Campus de Parnaíba, Universidade Federal do Piauí, Parnaíba, PI, Brazil.|Curso de Ciências da Natureza, Universidade Federal do Maranhão (UFMA), Grajaú, MA, Brazil.
authors.forename: Jefferson A
authors.initials: JA
authors.lastname: Rocha
authors.affiliation: Programa de Mestrado em Biotecnologia (PPGBiotec), Campus de Parnaíba, Universidade Federal do Piauí (UFPI), Parnaíba, PI, Brazil.|Núcleo de Pesquisa em Biodiversidade e Biotecnologia, Biotec, Campus de Parnaíba, Universidade Federal do Piauí, Parnaíba, PI, Brazil.
authors.forename: Ivanilza M
authors.initials: IM
authors.lastname: Andrade
authors.affiliation: Núcleo de Pesquisa em Biodiversidade e Biotecnologia, Biotec, Campus de Parnaíba, Universidade Federal do Piauí, Parnaíba, PI, Brazil.
authors.forename: Leiz M C
authors.initials: LM
authors.lastname: Véras
authors.affiliation: Núcleo de Pesquisa em Biodiversidade e Biotecnologia, Biotec, Campus de Parnaíba, Universidade Federal do Piauí, Parnaíba, PI, Brazil.|Programa de Pós-graduação da Rede Nordeste de Biotecnologia, RENORBIO, Ponto focal UFPI, Teresina, Piauí, Brazil.
authors.forename: Patrick V
authors.initials: PV
authors.lastname: Quelemes
authors.affiliation: Colegiado Acadêmico de Medicina. Campus Paulo Afonso, Universidade Federal do Vale do São Francisco (UNIVASF), Petrolina, Brazil.
authors.forename: David F
authors.initials: DF
authors.lastname: Lima
authors.affiliation: Departamento de Morfofisiologia Veterinária, Universidade Federal do Piauí, Teresina, PI, Brazil.
authors.forename: Maria J S
authors.initials: MJ
authors.lastname: Soares
authors.affiliation: Núcleo de Enteroparasitas, Instituto Adolfo Lutz, São Paulo, SP, Brazil.
authors.forename: Pedro L S
authors.initials: PL
authors.lastname: Pinto
authors.affiliation: Royal Botanic Gardens, Kew, Richmond, Surrey, TW9 3AE, UK.
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Mayo
authors.affiliation: UCIBIO-REQUIMTE, Departamento de Química e Bioquímica, Universidade do Porto, Porto, Portugal.
authors.forename: Galya
authors.initials: G
authors.lastname: Ivanova
authors.affiliation: UCIBIO-REQUIMTE, Departamento de Química e Bioquímica, Universidade do Porto, Porto, Portugal.
authors.forename: Maria
authors.initials: M
authors.lastname: Rangel
authors.affiliation: LAQV/REQUIMTE, Instituto Superior de Engenharia do Porto, Instituto Politécnico do Porto, Porto, Portugal.
authors.forename: Manuela
authors.initials: M
authors.lastname: Correia
authors.affiliation: Instituto de Física de São Carlos, Universidade de São Paulo, São Carlos, SP, Brazil.
authors.forename: Ana Carolina
authors.initials: AC
authors.lastname: Mafud
authors.affiliation: Instituto de Física de São Carlos, Universidade de São Paulo, São Carlos, SP, Brazil.
authors.forename: Yvonne P
authors.initials: YP
authors.lastname: Mascarenhas
authors.affiliation: LAQV/REQUIMTE, Instituto Superior de Engenharia do Porto, Instituto Politécnico do Porto, Porto, Portugal.
authors.forename: Cristina
authors.initials: C
authors.lastname: Delerue-Matos
authors.affiliation: Núcleo de Pesquisa em Doenças Negligenciadas, Universidade Guarulhos (NPDN/UNG), Guarulhos, SP, Brazil.
authors.forename: Josué
authors.initials: J
authors.lastname: de Moraes
authors.affiliation: UCIBIO-REQUIMTE, Departamento de Química e Bioquímica, Universidade do Porto, Porto, Portugal.
authors.forename: Peter
authors.initials: P
authors.lastname: Eaton
authors.affiliation: Núcleo de Pesquisa em Biodiversidade e Biotecnologia, Biotec, Campus de Parnaíba, Universidade Federal do Piauí, Parnaíba, PI, Brazil.|Area Morfologia, Faculdade de Medicina, Universidade de Brasília (UnB), Brasília, DF, Brazil.
authors.forename: José R S A
authors.identifier: http://orcid.org/0000-0002-1096-3236
authors.initials: JR
authors.lastname: Leite
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives; D000470:Alkaloids / Q000737:chemistry*; D000818:Animals; D000871:Anthelmintics / Q000737:chemistry*; D000900:Anti-Bacterial Agents / Q000737:chemistry*; D007093:Imidazoles / Q000737:chemistry* / Q000494:pharmacology; D032103:Pilocarpus / Q000737:chemistry*; D010936:Plant Extracts / Q000737:chemistry*; D018515:Plant Leaves / Q000737:chemistry*; D014709:Vero Cells
chemical_list: D000470:Alkaloids; D000871:Anthelmintics; D000900:Anti-Bacterial Agents; D007093:Imidazoles; D010936:Plant Extracts; C575691:epiisopiloturine; C029899:imidazole; D015107:4-Butyrolactone
keywords: anthelmintic activity; epiisopilosine; imidazole alkaloids; pilocarpus microphyllus; schistosoma mansoni