{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T23:35:07Z","timestamp":1771457707083,"version":"3.50.1"},"reference-count":47,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,5,8]],"date-time":"2023-05-08T00:00:00Z","timestamp":1683504000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"PT national funds","award":["UIDB\/50006\/2020"],"award-info":[{"award-number":["UIDB\/50006\/2020"]}]},{"name":"PT national funds","award":["UIDB\/04423\/2020"],"award-info":[{"award-number":["UIDB\/04423\/2020"]}]},{"name":"PT national funds","award":["UIDP\/04423\/2020"],"award-info":[{"award-number":["UIDP\/04423\/2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Pest resistance against fungicides is a widespread and increasing problem, with impact on crop production and public health, making the development of new fungicides an urgent need. Chemical analyses of a crude methanol extract (CME) of Guiera senegalensis leaves revealed the presence of sugars, phospholipids, phytosterols, guieranone A, porphyrin-containing compounds, and phenolics. To connect chemical composition with biological effects, solid-phase extraction was used to discard water-soluble compounds with low affinity for the C18 matrix and obtain an ethyl acetate fraction (EAF) that concentrates guieranone A and chlorophylls, and a methanol fraction (MF) dominated by phenolics. While the CME and MF exhibited poor antifungal activity against Aspergillus fumigatus, Fusarium oxysporum and Colletotrichum gloeosporioides, the EAF demonstrated antifungal activity against these filamentous fungi, particularly against C. gloeosporioides. Studies with yeasts revealed that the EAF has strong effectiveness against Saccharomyces cerevisiae, Cryptococcus neoformans and Candida krusei with MICs of 8, 8 and 16 \u03bcg\/mL, respectively. A combination of in vivo and in vitro studies shows that the EAF can function as a mitochondrial toxin, compromising complexes I and II activities, and as a strong inhibitor of fungal tyrosinase (Ki = 14.40 \u00b1 4.49 \u00b5g\/mL). Thus, EAF appears to be a promising candidate for the development of new multi-target fungicides.<\/jats:p>","DOI":"10.3390\/antibiotics12050869","type":"journal-article","created":{"date-parts":[[2023,5,9]],"date-time":"2023-05-09T02:28:08Z","timestamp":1683599288000},"page":"869","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Antifungal Activity of Guiera senegalensis: From the Chemical Composition to the Mitochondrial Toxic Effects and Tyrosinase Inhibition"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6964-8110","authenticated-orcid":false,"given":"Rute","family":"Moreira","sequence":"first","affiliation":[{"name":"REQUIMTE\/LAQV, Laborat\u00f3rio de Farmacognosia, Departamento de Qu\u00edmica, Faculdade de Farm\u00e1cia, Universidade do Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8682-0004","authenticated-orcid":false,"given":"Federico","family":"Ferreres","sequence":"additional","affiliation":[{"name":"Molecular Recognition and Encapsulation (REM) Group, Department of Food Technology and Nutrition, Universidad Cat\u00f3lica de Murcia, 30107 Murcia, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7646-0386","authenticated-orcid":false,"given":"\u00c1ngel","family":"Gil-Izquierdo","sequence":"additional","affiliation":[{"name":"Research Group on Quality, Safety and Bioactivity of Plant Foods, Department of Food Science and Technology, CEBAS (CSIC), Campus University Espinardo, 30100 Murcia, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8727-9678","authenticated-orcid":false,"given":"Nelson G. M.","family":"Gomes","sequence":"additional","affiliation":[{"name":"REQUIMTE\/LAQV, Laborat\u00f3rio de Farmacognosia, Departamento de Qu\u00edmica, Faculdade de Farm\u00e1cia, Universidade do Porto, 4050-313 Porto, Portugal"}]},{"given":"Lu\u00edsa","family":"Ara\u00fajo","sequence":"additional","affiliation":[{"name":"MDS\u2014Medicamentos e Diagn\u00f3sticos em Sa\u00fade, Avenida dos Combatentes da Liberdade da P\u00e1tria, Bissau, Guinea-Bissau"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2948-5809","authenticated-orcid":false,"given":"Eug\u00e9nia","family":"Pinto","sequence":"additional","affiliation":[{"name":"Laboratory of Microbiology, Biological Sciences Department, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"},{"name":"Interdisciplinary Centre of Marine and Environmental Research (CIIMAR), University of Porto, 4450-208 Matosinhos, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9764-3920","authenticated-orcid":false,"given":"Paula B.","family":"Andrade","sequence":"additional","affiliation":[{"name":"REQUIMTE\/LAQV, Laborat\u00f3rio de Farmacognosia, Departamento de Qu\u00edmica, Faculdade de Farm\u00e1cia, Universidade do Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4170-0092","authenticated-orcid":false,"given":"Romeu A.","family":"Videira","sequence":"additional","affiliation":[{"name":"REQUIMTE\/LAQV, Laborat\u00f3rio de Farmacognosia, Departamento de Qu\u00edmica, Faculdade de Farm\u00e1cia, Universidade do Porto, 4050-313 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,8]]},"reference":[{"key":"ref_1","unstructured":"(2023, January 10). Eurostat Sales of Pesticides in the EU. Available online: https:\/\/ec.europa.eu\/eurostat\/web\/products-eurostat-news\/-\/ddn-20200603-1."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.bcp.2016.11.019","article-title":"Antifungals","volume":"133","author":"Campoy","year":"2017","journal-title":"Biochem. Pharmacol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"143","DOI":"10.15698\/mic2020.06.718","article-title":"Fungal infections in humans: The silent crisis","volume":"7","author":"Kainz","year":"2020","journal-title":"Microb. Cell"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1021\/np0204904","article-title":"Guieranone A, a naphthyl butenone from the leaves of Guiera senegalensis with antifungal activity","volume":"66","author":"Silva","year":"2003","journal-title":"J. Nat. Prod."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/S0944-7113(97)80007-4","article-title":"Guiera senegalensis J. F. Gmelin (Combretaceae): Biological activities and chemical investigation","volume":"3","author":"Bosisio","year":"1997","journal-title":"Phytomedicine"},{"key":"ref_6","first-page":"006","article-title":"GC-MS analysis and antifungal activity from galls of Guiera senegalensis J.F Gmel (Combretaceae)","volume":"3","author":"Konate","year":"2013","journal-title":"J. Appl. Pharm. Sci."},{"key":"ref_7","first-page":"208","article-title":"Phytochemical screening and anti-TB activity of root extracts of Guiera senegalensis (J. F. Gmel)","volume":"3","author":"Adebiyi","year":"2015","journal-title":"Am. J. Biosci. Bioeng."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.jep.2005.12.030","article-title":"Phytochemical and pharmacological study of roots and leaves of Guiera senegalensis J.F. Gmel (Combretaceae)","volume":"106","author":"Fiot","year":"2006","journal-title":"J. Ethnopharmacol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/S0076-6879(99)99017-1","article-title":"Analysis of total phenols and other oxidation substrates and antioxidants by means of folin-ciocalteu reagent","volume":"299","author":"Singleton","year":"1999","journal-title":"Methods Enzymol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"C80","DOI":"10.1111\/j.1750-3841.2011.02477.x","article-title":"Reutilization of mango byproducts: Study of the effect of extraction solvent and temperature on their antioxidant properties","volume":"77","author":"Dorta","year":"2012","journal-title":"J. Food Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1021\/ac60111a017","article-title":"Colorimetric method for determination of sugars and related substances","volume":"28","author":"Dubois","year":"1956","journal-title":"Anal. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.3233\/JAD-141002","article-title":"Cardiolipin profile changes are associated to the early synaptic mitochondrial dysfunction in Alzheimer\u2019s Disease","volume":"43","author":"Oliveira","year":"2014","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1042\/bj0520611","article-title":"The determination of cholesterol by the Liebermann-Burchard reaction","volume":"52","author":"Kenny","year":"1952","journal-title":"Biochem. J."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"F4.3.1","DOI":"10.1002\/0471142913.faf0403s01","article-title":"Chlorophylls and carotenoids: Measurement and characterization by UV-Vis spectroscopy","volume":"1","author":"Lichtenthaler","year":"2001","journal-title":"Curr. Protoc. Food Anal. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1002\/ptr.1025","article-title":"Antimalarial activity of extracts and alkaloids isolated from six plants used in traditional medicine in Mali and Sao Tome","volume":"16","author":"Ancolio","year":"2002","journal-title":"Phyther. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1007\/s004360100454","article-title":"Synergistic in vitro antimalarial activity of plant extracts used as traditional herbal remedies in Mali","volume":"88","author":"Azas","year":"2002","journal-title":"Parasitol. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1002\/(SICI)1099-1565(200001\/02)11:1<52::AID-PCA482>3.0.CO;2-D","article-title":"HPLC isolation, identification and quantification of tannins from Guiera senegalensis","volume":"11","author":"Bouchet","year":"2000","journal-title":"Phytochem. Anal."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1080\/13880209.2017.1300175","article-title":"Quantitative analysis of rutin, quercetin, naringenin, and gallic acid by validated RP- and NP-HPTLC methods for quality control of anti-HBV active extract of Guiera senegalensis","volume":"55","author":"Alam","year":"2017","journal-title":"Pharm. Biol."},{"key":"ref_19","first-page":"1","article-title":"Phenolic compounds as potent free radical scavenging and enzyme inhibitory components from the leaves of Guiera senegalensis","volume":"14","author":"Dirar","year":"2019","journal-title":"Nat. Prod. Commun."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1021\/jf00039a026","article-title":"Isolation of tannins from leaves of some trees and shrubs and their properties","volume":"42","author":"Makkar","year":"1994","journal-title":"J. Agric. Food Chem."},{"key":"ref_21","first-page":"69","article-title":"Flavonoids of Guiera senegalensis J. F. GMEL.\u2014Thin-layer chromatography and numerical methods","volume":"71","author":"Bucar","year":"1998","journal-title":"Croat. Chem. Acta"},{"key":"ref_22","first-page":"454","article-title":"Isolation and characterization of Guiera senegalensis J.F.Gmel. active principles","volume":"136","author":"Ficarra","year":"1997","journal-title":"Boll. Chim. Farm."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.jep.2004.09.016","article-title":"Inhibition of fowlpox virus by an aqueous acetone extract from galls of Guiera senegalensis J. F. Gmel (Combretaceae)","volume":"96","author":"Lamien","year":"2005","journal-title":"J. Ethnopharmacol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"842","DOI":"10.2174\/1385272821666170920164836","article-title":"Mass Spectrometry of non-allomerized chlorophylls a and b derivatives from plants","volume":"22","author":"Viera","year":"2018","journal-title":"Curr. Org. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1105\/tpc.108.064089","article-title":"Pheophytin pheophorbide hydrolase (pheophytinase) is involved in chlorophyll breakdown during leaf senescence in Arabidopsis","volume":"21","author":"Schelbert","year":"2009","journal-title":"Plant Cell"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.cropro.2013.02.016","article-title":"Epidemiology of cashew anthracnose (Colletotrichum gloeosporioides Penz.) in Mozambique","volume":"49","author":"Uaciquete","year":"2013","journal-title":"Crop Prot."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1078\/0944-5013-00186","article-title":"Comparison of cross inoculation potential of South African avocado and mango isolates of Colletotrichum gloeosporioides","volume":"158","author":"Sanders","year":"2003","journal-title":"Microbiol. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"105049","DOI":"10.1016\/j.pestbp.2022.105049","article-title":"Sensitivity to fungicides in isolates of Colletotrichum gloeosporioides and C. acutatum species complexes and efficacy against anthracnose diseases","volume":"182","author":"Ishii","year":"2022","journal-title":"Pestic. Biochem. Physiol."},{"key":"ref_29","first-page":"36","article-title":"Antimicrobial activity of chlorophyll-based solution on Candida albicans and Enterococcus faecalis","volume":"4","author":"Maekawa","year":"2007","journal-title":"Rev. Sul-Bras. Odontol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1016\/j.dyepig.2017.09.073","article-title":"Synthesis and investigation of water-soluble chlorophyll pigments for antimicrobial photodynamic therapy","volume":"149","author":"Kustov","year":"2018","journal-title":"Dye. Pigment."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1039\/C9NP00011A","article-title":"Synergy and antagonism in natural product extracts: When 1 + 1 does not equal 2","volume":"36","author":"Caesar","year":"2019","journal-title":"Nat. Prod. Rep."},{"key":"ref_32","unstructured":"Silva, M.G., Mendes, D., Manuel Oliveira, M., Andrade, P.B., Videira, R.A., and Peixoto, F. (2023). Mitochondrial Intoxication, Elsevier."},{"key":"ref_33","first-page":"3","article-title":"Bin Mitochondrial electron transport chain, ROS generation and uncoupling","volume":"44","author":"Zhao","year":"2019","journal-title":"Int. J. Mol. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"128114","DOI":"10.1016\/j.bmcl.2021.128114","article-title":"Novel trifluoromethyl sydnone derivatives: Design, synthesis and fungicidal activity","volume":"44","author":"Du","year":"2021","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_35","unstructured":"Buhler, W. (2023, February 15). Raised Resistance Risks. Available online: https:\/\/pesticidestewardship.org\/resistance\/fungicide-resistance\/raised-resistance-risks\/."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1002\/ps.565","article-title":"Mechanisms influencing the evolution of resistance to Qo inhibitor fungicides","volume":"58","author":"Gisi","year":"2002","journal-title":"Pest Manag. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2107","DOI":"10.1002\/ps.5264","article-title":"Mitochondrial complex III Qi-site inhibitor resistance mutations found in laboratory selected mutants and field isolates","volume":"75","author":"Mounkoro","year":"2019","journal-title":"Pest Manag. Sci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.sajb.2016.12.013","article-title":"Anti-tyrosinase, total phenolic content and antioxidant activity of selected Sudanese medicinal plants","volume":"109","author":"Muddathir","year":"2017","journal-title":"S. Afr. J. Bot."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.sajb.2018.07.003","article-title":"Effects of extraction solvents on total phenolic and flavonoid contents and biological activities of extracts from Sudanese medicinal plants","volume":"120","author":"Dirar","year":"2019","journal-title":"S. Afr. J. Bot."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1002\/bmb.20887","article-title":"Mushroom tyrosinase: A model system to combine experimental investigation of enzyme-catalyzed reactions, data handling using R, and enzyme-inhibitor structural studies","volume":"43","author":"Nairn","year":"2015","journal-title":"Biochem. Mol. Biol. Educ."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.foodchem.2014.04.070","article-title":"Phenolic profile of Douro wines and evaluation of their NO scavenging capacity in LPS-stimulated RAW 264.7 macrophages","volume":"163","author":"Rebelo","year":"2014","journal-title":"Food Chem."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Nielsen, S.S. (2010). Food Analysis Laboratory Manual, Springer.","DOI":"10.1007\/978-1-4419-1463-7"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/0003-2697(70)90343-X","article-title":"Spectrophotometric determination of phosphate esters in the presence and absence of orthophosphate","volume":"36","author":"Bartlett","year":"1970","journal-title":"Anal. Biochem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1590\/S0102-695X2013000500004","article-title":"Total phytosterol content in drug materials and extracts from roots of Acanthospermum hispidum by UV-VIS spectrophotometry","volume":"23","author":"Silva","year":"2013","journal-title":"Rev. Bras. Farmacogn."},{"key":"ref_45","unstructured":"Costa, A.F. (2001). Farmacognosia\u2014Volume III, Funda\u00e7\u00e3o Calouste Gulbenkian. [3rd ed.]."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/j.indcrop.2015.09.006","article-title":"Comparing the phenolic profile of Pilocarpus pennatifolius Lem. by HPLC\u2013DAD\u2013ESI\/MS n with respect to authentication and enzyme inhibition potential","volume":"77","author":"Ferreres","year":"2015","journal-title":"Ind. Crop. Prod."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1007\/s11306-016-1082-x","article-title":"Untargeted metabolomics approach using UPLC-ESI-QTOF-MS to explore the metabolome of fresh-cut iceberg lettuce","volume":"12","author":"Garcia","year":"2016","journal-title":"Metabolomics"}],"container-title":["Antibiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6382\/12\/5\/869\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:31:34Z","timestamp":1760124694000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6382\/12\/5\/869"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,8]]},"references-count":47,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2023,5]]}},"alternative-id":["antibiotics12050869"],"URL":"https:\/\/doi.org\/10.3390\/antibiotics12050869","relation":{},"ISSN":["2079-6382"],"issn-type":[{"value":"2079-6382","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,8]]}}}