{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T04:17:04Z","timestamp":1785471424330,"version":"3.56.0"},"reference-count":41,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2014,11,4]],"date-time":"2014-11-04T00:00:00Z","timestamp":1415059200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Fusarium disease causes considerable losses in the cultivation of Piper nigrum, the black pepper used in the culinary world. Brazil was the largest producer of black pepper, but in recent years has lost this hegemony, with a significant reduction in its production, due to the ravages produced by the Fusarium solani f. sp. piperis, the fungus which causes this disease. Scientific research seeks new alternatives for the control and the existence of other Piper species in the Brazilian Amazon, resistant to disease, are being considered in this context. The main constituents of the oil of Piper divaricatum are methyleugenol (75.0%) and eugenol (10.0%). The oil and these two main constituents were tested individually at concentrations of 0.25 to 2.5 mg\/mL against F. solani f. sp. piperis, exhibiting strong antifungal index, from 18.0% to 100.0%. The 3D structure of the \u03b2-glucosidase from Fusarium solani f. sp. piperis, obtained by homology modeling, was used for molecular docking and molecular electrostatic potential calculations in order to determine the binding energy of the natural substrates glucose, methyleugenol and eugenol. The results showed that \u03b2-glucosidase (Asp45, Arg113, Lys146, Tyr193, Asp225, Trp226 and Leu99) residues play an important role in the interactions that occur between the protein-substrate and the engenol and methyleugenol inhibitors, justifying the antifungal action of these two phenylpropenes against Fusarium solani f. sp. piperis.<\/jats:p>","DOI":"10.3390\/molecules191117926","type":"journal-article","created":{"date-parts":[[2014,11,4]],"date-time":"2014-11-04T09:41:15Z","timestamp":1415094075000},"page":"17926-17942","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Antifungal Activity and Computational Study of Constituents from Piper divaricatum Essential Oil against Fusarium Infection in Black Pepper"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9351-876X","authenticated-orcid":false,"given":"Joyce","family":"Da Silva","sequence":"first","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Biotecnologia, Instituto de Ci\u00eancias Biol\u00f3gicas,  Universidade Federal do Par\u00e1, Bel\u00e9m, PA 66075-110, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2310-5107","authenticated-orcid":false,"given":"Jos\u00e9","family":"Silva","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Planejamento e Desenvolvimento de F\u00e1rmacos, Instituto de Ci\u00eancias Exatas e Naturais, Universidade Federal do Par\u00e1, Bel\u00e9m, PA 66075-110, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soelange","family":"Nascimento","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Planejamento e Desenvolvimento de F\u00e1rmacos, Instituto de Ci\u00eancias Exatas e Naturais, Universidade Federal do Par\u00e1, Bel\u00e9m, PA 66075-110, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shirlley","family":"Da Luz","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Biotecnologia, Instituto de Ci\u00eancias Biol\u00f3gicas,  Universidade Federal do Par\u00e1, Bel\u00e9m, PA 66075-110, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erisl\u00e9ia","family":"Meireles","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Biotecnologia, Instituto de Ci\u00eancias Biol\u00f3gicas,  Universidade Federal do Par\u00e1, Bel\u00e9m, PA 66075-110, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cl\u00e1udio","family":"Alves","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Planejamento e Desenvolvimento de F\u00e1rmacos, Instituto de Ci\u00eancias Exatas e Naturais, Universidade Federal do Par\u00e1, Bel\u00e9m, PA 66075-110, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Ramos","sequence":"additional","affiliation":[{"name":"Instituto de Estudos em Sa\u00fade e Biol\u00f3gicas, Universidade Federal do Sul e Sudeste do Par\u00e1, Marab\u00e1, PA 68501-970, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9","family":"Maia","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Qu\u00edmica, Instituto de Ci\u00eancias Exatas e Naturais,  Universidade Federal do Par\u00e1, Bel\u00e9m, PA 66075-110, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2014,11,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Nair, K.P.P. (2011). Agronomy and Economy of Black Pepper and Cardamom: The \u201cKing\u201d and \u201cQueen\u201d of Spices, Elsevier.","DOI":"10.1016\/B978-0-12-391865-9.00002-5"},{"key":"ref_2","unstructured":"Lemos, O.F., Poltronieri, M.C., Rodrigues, S.M., Menezes, I.C., and Mondin, M. (2011). Conserva\u00e7\u00e3o e Melhoramento Gen\u00e9tico da Pimenteira-do-reino (Piper nigrum L.) Associado \u00e0s T\u00e9cnicas de Biotecnologia, Embrapa Amaz\u00f4nia Oriental."},{"key":"ref_3","unstructured":"Duarte, M.L.R. (1999). Doen\u00e7as de Plantas no Tr\u00f3pico \u00damido, Embrapa Amaz\u00f4nia Oriental."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1590\/1809-43922001313348","article-title":"Resist\u00eancia de piper\u00e1ceas nativas da Amaz\u00f4nia \u00e0 infec\u00e7\u00e3o causada por Nectria haematococca f. sp. piperis","volume":"31","author":"Albuquerque","year":"2001","journal-title":"Acta Amaz."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.1590\/S0103-50532005000800022","article-title":"Divergence of secondary metabolism in cell suspension cultures and differentiated plants of Piper cernuum and P. crassinervium","volume":"16","author":"Danelutte","year":"2005","journal-title":"J. Braz. Chem. Soc."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.phytol.2009.01.001","article-title":"Prenylated benzoic acid derivatives from Piper aduncum L. and P. hostmannianum C. DC. (Piperaceae)","volume":"2","author":"Lago","year":"2009","journal-title":"Phytochem. Lett."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Peter, P.K. (2004). Handbook of Herbs and Spices, CRC Press, Taylor & Francis Group.","DOI":"10.1533\/9781855738355"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1080\/10412905.1993.9698217","article-title":"Gas chromatographic analysis and odor profiles of few Indian genotypes of Piper nigrum L.","volume":"5","author":"Gopalakrishnan","year":"1993","journal-title":"J. Essent. Oil Res."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Parthasarathy, V.A., Chempakam, B., and Zachariah, T.J. (2008). Chemistry of Spices, CABI.","DOI":"10.1079\/9781845934057.0000"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1016\/j.scienta.2009.09.017","article-title":"Correlation of metabolites in the leaf and berries of selected black pepper varieties","volume":"123","author":"Zachariah","year":"2010","journal-title":"Sci. Hortic."},{"key":"ref_11","first-page":"477","article-title":"Essential oil composition, antioxidant capacity and antifungal activity of Piper divaricatum","volume":"5","author":"Silva","year":"2010","journal-title":"Nat. Prod. Commun."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1429","DOI":"10.2174\/092986609789839368","article-title":"Identifying sequences potentially related to resistance response of Piper tuberculatum to Fusarium solani f. sp. piperis by suppression subtractive hybridization","volume":"16","author":"Nascimento","year":"2009","journal-title":"Protein Pept. Lett."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2553","DOI":"10.1007\/s11738-011-0788-7","article-title":"Identification of sequences expressed during compatible Black pepper-Fusarium solani f. sp. peperis interaction","volume":"33","author":"Costa","year":"2011","journal-title":"Acta Physiol. Plant."},{"key":"ref_14","first-page":"200","article-title":"Esp\u00e9cies de Piper da Amaz\u00f4nia ricas em safrol","volume":"10","author":"Maia","year":"1987","journal-title":"Quim. Nova"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1002\/(SICI)1099-1026(1998070)13:4<269::AID-FFJ744>3.0.CO;2-A","article-title":"Constituents of the essential oil of Piper aduncum L. growing wild in the Amazon region","volume":"13","author":"Maia","year":"1998","journal-title":"Flavour Fragr. J."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1002\/cbdv.200890011","article-title":"Variability in essential oil composition of Piper marginatum sensu lato","volume":"5","author":"Andrade","year":"2008","journal-title":"Chem. Biodivers."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.1002\/cbdv.200800212","article-title":"Chemical variation in Piper aduncum and biological properties of its dillapiole rich essential oil","volume":"6","author":"Almeida","year":"2009","journal-title":"Chem. Biodivers."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1590\/S0100-41582007000200008","article-title":"Atividade antif\u00fangica de \u00f3leos essenciais de esp\u00e9cies de Piper sobre Crinipellis perniciosa, Phytophthora palmivora e Phytophthora capsici","volume":"32","author":"Silva","year":"2007","journal-title":"Fitopatol. Bras."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"6989","DOI":"10.1021\/jf020466w","article-title":"Antifungal constituents of the essential oil fraction of Artemisia dracunculus L. var. dracunculus","volume":"50","author":"Meepagala","year":"2002","journal-title":"J. Agric. Food Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.cropro.2009.12.007","article-title":"Activities of essential oils from Asarum heterotropoides var. mandshuricum against five phytopathogens","volume":"29","author":"Dan","year":"2010","journal-title":"Crop Prot."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1016\/j.ijfoodmicro.2009.10.008","article-title":"Activity of natural compounds on Fusarium verticillioides and fumonisin production in stored maize kernels","volume":"136","author":"Menniti","year":"2010","journal-title":"Int. J. Food Microbiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/j.biortech.2006.11.022","article-title":"Synergistic effects of cinnamaldehyde in combination with eugenol against wood decay fungi","volume":"99","author":"Yen","year":"2008","journal-title":"Bioresour. Technol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.ijfoodmicro.2004.03.022","article-title":"Essential oils: Their antibacterial properties and potential applications in foods\u2014A review","volume":"94","author":"Burt","year":"2004","journal-title":"Int. J. Food Microbiol."},{"key":"ref_24","unstructured":"Burges, H.D., and Hussey, N.W. (1971). Microbial Control of Insects and Mites, Academic Press."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1093\/bioinformatics\/bti770","article-title":"The SWISS-MODEL workspace: A web-based environment for protein structure homology modeling","volume":"22","author":"Arnold","year":"2006","journal-title":"Bioinformatics"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1006\/jmbi.1993.1626","article-title":"Comparative protein modeling by satisfaction of spatial restraints","volume":"234","author":"Sali","year":"1993","journal-title":"J. Mol. Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1042\/BJ20100351","article-title":"Role of a PA14 domain in determining substrate specificity of a glycoside hydrolase family 3 \u03b2-glucosidase from Kluyveromyces marxianus","volume":"431","author":"Yoshida","year":"2010","journal-title":"Biochem. J."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1107\/S0021889892009944","article-title":"PROCHECK: A program to check the stereochemical quality of protein structures","volume":"26","author":"Laskowski","year":"1993","journal-title":"J. Appl. Crystallogr."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1093\/bioinformatics\/btq662","article-title":"Toward the estimation of the absolute quality of individual protein structure models","volume":"27","author":"Benkert","year":"2011","journal-title":"Bioinformatics"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2775","DOI":"10.1021\/ci2006005","article-title":"Computational analysis of human OGA structure in complex with PUGNAc and NAG-Thiazoline derivatives","volume":"52","author":"Alencar","year":"2012","journal-title":"J. Chem. Inf. Model."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2782","DOI":"10.1039\/b618225a","article-title":"On the nature of hydrogen bonds: An overview on computational studies and a word about patterns","volume":"9","author":"Rozas","year":"2007","journal-title":"Phys. Chem. Chem. Phys."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3398","DOI":"10.1002\/qua.24253","article-title":"Insights for design of Tripanosoma cruzi GAPDH inhibitors: A QM\/MM MD of 1,3-bisphospho-D-glyceric acid analogs","volume":"112","author":"Silva","year":"2012","journal-title":"Int. J. Quantum Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.cplett.2013.08.006","article-title":"Metal-dependent inhibition of HIV-1 integrase by 5CITEP inhibitor: A theoretical QM\/MM approach","volume":"583","author":"Nascimento","year":"2013","journal-title":"Chem. Phys. Lett."},{"key":"ref_34","unstructured":"Adams, R.P. (2007). Identification of Essencial Oil Components by Gas Chromatography\/Mass Spectrometry, Allured Publ. Corp.. [4th ed.]."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1584\/jpestics.19.4_299","article-title":"Synthesis and fungicidal activity of new 1,3,2-oxazaphospholidine2-sulfides","volume":"19","author":"Taira","year":"1994","journal-title":"J. Pestic. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1146\/annurev.biophys.29.1.291","article-title":"Comparative protein structure modeling of genes and genomes","volume":"29","author":"Stuart","year":"2000","journal-title":"Annu. Rev. Biophys. Biomol. Struct."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1007\/s00894-011-1145-x","article-title":"Homology modeling, molecular dynamics and QM\/MM study of the regulatory protein PhoP from Corynebacterium pseudotuberculosis","volume":"18","author":"Moraes","year":"2012","journal-title":"J. Mol. Model."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Coleman, J.J., Rounsley, S.D., Rodriguez-Carres, M., Kuo, A., Wasmann, C.C., Grimwood, J., Schmutz, J., Taga, M., White, G.J., and Zhou, S. (2009). The Genome of Nectria haematococca: Contribution of supernumerary chromosomes to gene expansion. PLoS Genet., 5.","DOI":"10.1371\/journal.pgen.1000618"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3315","DOI":"10.1021\/jm051197e","article-title":"MolDock: A new technique for high-accuracy molecular docking","volume":"49","author":"Thomsen","year":"2006","journal-title":"J. Med. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1002\/1096-987X(20001130)21:15<1319::AID-JCC1>3.0.CO;2-8","article-title":"Adaptive multilevel finite element solution of the Poisson-Boltzmann equation I. Algorithms and examples","volume":"21","author":"Holst","year":"2000","journal-title":"J. Comput. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"W665","DOI":"10.1093\/nar\/gkh381","article-title":"PDB2PQR: An automated pipeline for the setup, execution, and analysis of Poisson-Boltzmann electrostatics calculations","volume":"32","author":"Dolinsky","year":"2004","journal-title":"Nucleic Acids Res."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/19\/11\/17926\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T21:08:53Z","timestamp":1760216933000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/19\/11\/17926"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,11,4]]},"references-count":41,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2014,11]]}},"alternative-id":["molecules191117926"],"URL":"https:\/\/doi.org\/10.3390\/molecules191117926","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,11,4]]}}}