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Pisolithus (Basidiomycota) is a ubiquitous and widely distributed fungal genus in forest ecosystems, known for establishing ectomycorrhizal associations with a range of host plants, enhancing their growth, and conferring protection against biotic and abiotic stresses. Beyond ecological applications, Pisolithus yields bioactive compounds with medicinal potential. This comprehensive review explores the transversal biological activity of Pisolithus fungi, aiming to provide a thorough overview of their antimicrobial, anticancer, and antioxidant potential. The focus is on elucidating bioactive compounds within Pisolithus to trigger further research for innovative applications. Compounds from Pisolithus displayed antimicrobial activity against a broad spectrum of microorganisms, including antibiotic-resistant bacteria. The efficacy of Pisolithus-derived compounds matched established medications, emphasizing their therapeutic potential. In anticancer research, the triterpene pisosterol stood out with documented cytotoxicity against various cancer cell lines, showcasing promise for novel anticancer therapies. Pisolithus was also recognized as a potential source of antioxidants, with basidiocarps exhibiting high antioxidant activity. In vivo validation and comprehensive studies on a broader range of compounds, together with mechanistic insights into the mode of action of Pisolithus-derived compounds, are compelling areas for future research.<\/jats:p>","DOI":"10.3390\/microorganisms12030450","type":"journal-article","created":{"date-parts":[[2024,2,23]],"date-time":"2024-02-23T06:07:39Z","timestamp":1708668459000},"page":"450","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Exploring the Bioactive Potential of Pisolithus (Basidiomycota): Comprehensive Insights into Antimicrobial, Anticancer, and Antioxidant Properties for Innovative Applications"],"prefix":"10.3390","volume":"12","author":[{"given":"Rui S.","family":"Oliveira","sequence":"first","affiliation":[{"name":"Centre for Functional Ecology, Associate Laboratory TERRA, Department of Life Sciences, University of Coimbra, Cal\u00e7ada Martim de Freitas, 3000-456 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9697-5579","authenticated-orcid":false,"given":"Marco","family":"Preto","sequence":"additional","affiliation":[{"name":"Interdisciplinary Centre of Marine and Environmental Research (CIIMAR\/CIMAR), University of Porto, Terminal de Cruzeiros do Porto de Leix\u00f5es, Av. General Norton de Matos s\/n, 4450-208 Matosinhos, Portugal"}]},{"given":"Germana","family":"Santos","sequence":"additional","affiliation":[{"name":"School of Health, Polytechnic Institute of Porto (ESS\/P.PORTO), Rua Dr. Ant\u00f3nio Bernardino de Almeida 400, 4200-072 Porto, Portugal"}]},{"given":"Ana Margarida","family":"Silva","sequence":"additional","affiliation":[{"name":"School of Health, Polytechnic Institute of Porto (ESS\/P.PORTO), Rua Dr. Ant\u00f3nio Bernardino de Almeida 400, 4200-072 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3585-2417","authenticated-orcid":false,"given":"Vitor","family":"Vasconcelos","sequence":"additional","affiliation":[{"name":"Interdisciplinary Centre of Marine and Environmental Research (CIIMAR\/CIMAR), University of Porto, Terminal de Cruzeiros do Porto de Leix\u00f5es, Av. General Norton de Matos s\/n, 4450-208 Matosinhos, Portugal"},{"name":"Department of Biology, Faculty of Sciences, University of Porto (FCUP), Rua do Campo Alegre, Edif\u00edcio FC4, 4169-007 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9882-4651","authenticated-orcid":false,"given":"Ros\u00e1rio","family":"Martins","sequence":"additional","affiliation":[{"name":"Interdisciplinary Centre of Marine and Environmental Research (CIIMAR\/CIMAR), University of Porto, Terminal de Cruzeiros do Porto de Leix\u00f5es, Av. General Norton de Matos s\/n, 4450-208 Matosinhos, Portugal"},{"name":"School of Health, Polytechnic Institute of Porto (ESS\/P.PORTO), Rua Dr. Ant\u00f3nio Bernardino de Almeida 400, 4200-072 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1038\/s41573-020-00114-z","article-title":"Natural products in drug discovery: Advances and opportunities","volume":"20","author":"Atanasov","year":"2021","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Kumar, K., Mehra, R., Guin\u00e9, R.P.F., Lima, M.J., Kumar, N., Kaushik, R., Ahmed, N., Yadav, A.N., and Kumar, H. (2021). Edible mushrooms: A comprehensive review on bioactive compounds with health benefits and processing aspects. Foods, 10.","DOI":"10.3390\/foods10122996"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Egbuna, C., and Dable Tupas, G. (2020). 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