The essential oils (EOs) from aerial parts of Piper aduncum, P. callosum and P. marginatum, collected from the Amazon region of Brazil, were analyzed by GC-MS and then evaluated for their antifungal and anticholinesterase activities. The essential oils were dominated by phenylpropanoids, such as dillapiole (73.0%) in P. aduncum, safrole (66.0%) in P. callosum and 3,4-methylenedioxypropiophenone (21.8%) in P. marginatum. The analyzed oils showed low to moderate antifungal activity, with detection limits (DL) from 10 to 100 μg against Cladosporium cladosporioides and C. sphareospermum. In the anticholinesterase (AChE) evaluation, the oils of P. callosum (DL = 0.01 ng) and P. marginatum (DL = 0.01 ng) were one hundred times more potent than the standard physostigmine (DL = 1.0 ng). Molecular docking analysis showed that phenylpropanoids docked reasonably well with acetylcholinesterase and may be responsible for the anti-AChE activities of the Piper EOs. This is the first presentation about acetylcholinesterase inhibition by methylenedioxyphenyl-propanoids.
ParmarV.S., JainS.C., BishtK.S., JainR., TanejaP., JhaA., TyagiO.D., PrasadA.K., WengelJ., OlsenC.E., BollP.M. (1997) Phytochemistry of the genus Piper. Phytochemistry, 46, 597–673.
2.
(a) GuimarãesE.F., GiordanoL.C.S. (2004) Piperaceae do Nordeste Brasileiro I: Estado do Ceará. Rodriguesia, 55, 21–46; (b) Ramos LS, Da Silva ML, Luz AIR, Zoghbi MGB, Maia JGS. (1986) Essential oil of Piper marginatum. Journal of Natural Products, 49, 712–713; (c) Sumathikutty MA, Rao JM, Padmakumari KP, Narayanan CS. (1999) Essential oil constituents of some Piper species. Flavour and Fragrance Journal, 14, 279–282.
3.
(a) YunckerT.G. (1972) The Piperaceae of Brazil. Hoehnea, 2, 19–366; (b) Guimarães EF, Carvalho-Silva M, Monteiro D, Medeiros ES, Queiroz GA. Piperaceae in lista de espécies da flora do Brasil. Jardim Botânico do Rio de Janeiro. Disponível em: <http://floradobrasil.jbrj.gov.br/jabot/floradobrasil/FB12735>. Accessed on 04 Nov. 2015; (c) Andrade EHA, Guimarães EF, Maia JGS (2009) Variabilidade química em óleos essenciais de espécies de Piper da Amazônia, Belém, FEQ/UFPA, 448 p.
4.
IwuM.M. (1993) Handbook of Medicinal Plants.CRC Press, Boca Raton, Florida, USA.
5.
(a) BotsairsA.S. (1997) As fórmulas mágicas das plantas.Rio de Janeiro: Record: Nova Era. (b) Vieira LS (1991) Manual de Medicina Popular. A Fitoterapia da Amazônia. Faculdade de Ciências Agrárias do Pará, 248 p.
6.
PinedoM., RengifoE., CerrutiT. (1997) Plantas medicinales de la Amazonia Peruana, estudio de su uso y cultivo.Instituto de Investigaciones de la Amazonía Peruana, 304, Iquitos.
7.
MaiaJ.G.S., ZoghbiM.G.B., AndradeE.H.A. (2001) Plantas aromáticas da Amazônia e seus óleos essenciais, Museu Paraense Emlio Goeldi, Belém, 138 p.
8.
(a) MaiaJ.G.S., GreenC.L., MilchardM.J. (1993) New source of natural safrole. Flavor and Fragrance Journal, 18, 20–22; (b) Andrade EH, Carreira LM, da Silva MH, da Silva JD, Bastos CN, Sousa PJ, Guimarães EF, Maia JG. (2008) Variability in essential-oil composition of Piper marginatum sensu lato. Chemistry & Biodiversity, 5, 197–208. (c) da Silva JKR, Andrade EHA, Kato MJ, Carreira LMM, Grimarães EF, Maia JGS. (2011) Antioxidant capacity and larvicidal and antifungal activities of essential oils and extracts from Piper krukoffii. Natural Product Communications, 6, 1361–1366.
AlmeidaR.N., Agra de FátimaM., MaiorF.N.S., SousaD.P. (2011) Essential oils and their constituents: anticonvulsant activity. Molecules, 16, 2726–2742.
11.
Da SilveiraR.D.C., AndradeL.N., De OliveiraRdrb, De SousaD.P. (2014) A review on anti-inflammatory activity of phenylpropanoids found in essential oils. Molecules, 19, 1459–1480.
12.
(a) SuY-C, HoC-L. (2013) Composition, in-vitro anticancer, and antimicrobial activities of the leaf essential oil of Machilus mushaensis from Taiwan. Natural Product Communications, 8, 273–275; (b) Manjamalai A, Grace VMB. (2013). The chemotherapeutic effect of essential oil of Plectranthus amboinicus (Lour) on lung metastasis developed by B16F-10 cell line in C57BL/6 mice. Cancer Investigation, 31, 74–82.
13.
(a) Medina-HolguínA.L., Omar HolguínF., MichelettoS., GoehleS., SimonJ.A., O'ConnellM.A. (2008) Chemotypic variation of essential oils in the medicinal plant, Anemopsis californica. Phytochemistry, 69, 919–927; (b) Kathirvel P, Ravi S. (2012) Chemical composition of the essential oil from basil (Ocimum basilicum Linn.) and its in vitro cytotoxicity against HeLa and HEp-2 human cancer cell lines and NIH 3T3 mouse embryonic fibroblasts. Natural Product Research, 26, 1112–1118.
14.
NIST (National Institute of Standards, and Technology) (2005) Mass Spectral Library (NIST/EPA/NIH, V. 2.0d).The NIST Mass Spectrometry Data Center, Gaithersburg, USA.
15.
AdamsR.P. (2007) Identification of Essential Oil Components by Gas Chromatography/Mass Spectrometry, 4th ed. Allured Publishing Corp., Carol Stream, IL, USA.
16.
MaiaJ.G.S., ZoghbiM.G.B., AndradeE.H.A., SantosA.S., SilvaM.H.L., LuzA.I.R., BastosC.N. (1998) Constituents of the essential oil of Piper aduncum L. growing wild in the Amazon region. Flavour and Fragrance Journal, 13, 269–272.
17.
SoutoR.N., HaradaA.Y., AndradeE.H., MaiaJ.G. (2012) Insecticidal activity of Piper essential oils from the Amazon against the fire ant Solenopsis saevissima (Smith). (Hymenoptera: Formicidae). Neotropical Entomology, 41, 510–517.
18.
AlmeidaR.R.P., SoutoR.N.P., BastosC.N., SilvaM.H.L., MaiaG.S. (2009) Chemical variation in Piper aduncum and biological properties of its dillapiole-rich essential oil. Chemistry & Biodiversity, 6, 1427–1434.
19.
OliveiraG.L., CardosoS.K., LaraC.R.Jr., VieiraT.M., GuimarãesE.F., FigueiredoL.S., MartinsER5, MoreiraD.L., KaplanM.A. (2013) Chemical study and larvicidal activity against Aedes aegypti of essential oil of Piper aduncum L. (Piperaceae). Anais da Academia Brasileira de Ciências, 85, 1227–1234.
20.
OliveiraJ.C.S., DiasI.J.M., Da CâmaraC.A.G., SchwartzM.O.E. (2006) Volatile constituents of the leaf oils of Piper aduncum L. from different regions of Pernambuco (Northeast of Brazil). Journal of Essential Oil Research, 18, 557–559.
21.
NavickieneH.M.D., MorandimA.A., AlécioA.C., RegasiniL.O., BergamoD.C.B., TelascreaM., CavalheiroA.J., LopesM.N., BolzaniV.S., FurlanM., MarquesM.O.M., YoungM.C.M., KatoM.J. (2006) Composition and antifungal activity of essential oils from Piper aduncum, Piper arboreum and Piper tuberculatum. Química Nova, 29, 467–470.
22.
MaiaJ.G.S., SilvaM.H.L., LuzA.I.R., ZoghbiM.G.B., RamosL.S. (1987) Espécies de Piper da Amazônia ricas em safrol. Química Nova, 10, 200–204.
23.
Van Genderen MarcelH.P., LeclercqP.A., DelgadoH.S., KanjilalP.B., SinghR.S. (1999) Compositional analysis of the leaf oils of Piper callosum Ruiz & Pav. from Peru and Michelia montana Blume from India. Spectroscopy, 14, 51–59.
24.
VoglerB., NolettoJ.A., HaberW.A., SetzerW.N. (2006) Chemical constituents of the essential oils of three Piper species from Monteverde, Costa Rica. Journal of Essential Oil Bearing Plants, 9, 230–238.
25.
AutranE.S., NevesI.A., da SilvaC.S., SantosG.K., da CâmaraC.A., NavarroD.M. (2009) Chemical composition, oviposition deterrent and larvicidal activities against Aedes aegypti of essential oils from Piper marginatum Jacq. (Piperaceae). Bioresource Technology, 7, 2284–2288.
26.
Da SilvaJ.K., AndradeE.H., GuimarãesE.F., MaiaJ.G. (2010) Essential oil composition, antioxidant capacity and antifungal activity of Piper divaricatum. Natural Products Communications, 5, 477–480.
27.
RadulovićN.S., MladenovićM.Z., BlagojevićP.D., Stojanović-RadićZ.Z., Ilic-TomicT., SenerovicL., Nikodinovic-RunicJ. (2013) Toxic essential oils. Part III: identification and biological activity of new allylmethoxyphenyl esters from a Chamomile species (Anthemis segetalis Ten.). Food and Chemical Toxicology, 62, 554–565.
28.
ParkI.K. (2014) Fumigant toxicity of Oriental sweetgum (Liquidambar orientalis) and valerian (Valeriana wallichii) essential oils and their components, including their acetylcholinesterase inhibitory activity, against Japanese termites (Reticulitermes speratus). Molecules, 19, 12547–12558.
29.
PanY., HuangN., ChoS., MacKerellA.D. (2003) Consideration of molecular weight during compound selection in virtual target-based database screening. Journal of Chemical Information and Computer Science, 43, 267–272.
30.
Van den DoolH., KratzPdja. (1963) Generalization of the retention index system including linear temperature programmed gas–liquid partition chromatography. Journal of Chromatography A, 11, 463–471.
31.
MarstonA. (2011) Thin-layer chromatography with biological detection in phytochemistry. Journal of Chromatography A, 1218, 2676–2683.
32.
da SilvaJ.K.R., PintoL.C., BurbanoR.M.R., MontenegroR.C., GuimarãesE.F., AndradeE.H.A., MaiaJ.G.S. (2014) Essential oils of Amazon Piper species and their cytotoxic, antifungal, antioxidant and anti-cholinesterase activities. Industrial Crops and Products, 58, 55–60.
33.
SilvaN.N., SilvaJ.R., AlvesC.N., AndradeE.H., da SilvaJ.K., MaiaJ.G. (2014) Acetylcholinesterase inhibitory activity and molecular docking study of 1-nitro-2-phenylethane, the main constituent of Aniba canelilla essential oil. Chemical Biology and Drug Design, 84, 192–198.
34.
(a) CheungJ., RudolphM.J., BurshteynF., CassidyM.S., GaryE.N., LoveJ., FranklinM.C., HeightJ.J. (2012) Structures of human acetylcholinesterase in complex with pharmacologically important ligands. Journal of Medicinal Chemistry, 55, 10282–10286; (b) Cheung J, Gary EN, Shiomi K, Rosenberry TL. (2013) Structures of human acetylcholinesterase bound to dihydrotanshinone I and territrem B show peripheral site flexibility. ACS Medicinal Chemistry Letters, 4, 1091–1096.
35.
(a) NepovimovaE., UliassiE., KorabecnyJ., Peña-AltamiraL.E., SamezS., PesaresiA., GarciaG.E., BartoliniM., AndrisanoV., BergaminiC., FatoR., LambaD., RobertiM., KucaK., MontiB., BolognesiM.L. (2014) Multitarget drug design strategy: Quinone-tacrine hybrids designed to block amyloid-β aggregation and to exert anticholinesterase and antioxidant effects. Journal of Medicinal Chemistry, 57, 8576–8579; (b) Pesaresi A, Lamba D. (2016) Torpedo californica acetylcholinesterase in complex with a tacrine-nicotinamide hybrid inhibitor. To be published. DOI: 10.2210/pdb4x3c/pdb.
36.
ThomsenR., ChristensenM.H. (2006) MolDock: a new technique for high-accuracy molecular docking. Journal of Medicinal Chemistry, 49, 3315–3321.
37.
HalgrenT.A. (1996) Merck molecular force field. I. Basis, form, scope, parameterization, and performance of MMFF 94. Journal of Computational Chemistry, 17, 490–519.
