{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T20:16:07Z","timestamp":1775592967591,"version":"3.50.1"},"reference-count":38,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T00:00:00Z","timestamp":1756771200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T00:00:00Z","timestamp":1756771200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chemistry &amp;amp; Biodiversity"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The fungi\n                    <jats:italic>Fusarium guttiforme<\/jats:italic>\n                    and\n                    <jats:italic>Phytophthora palmivora<\/jats:italic>\n                    were cultivated in four different media (Potato Dextrose Agar, Czapek, rice, and ISP2) and co\u2010cultured to stimulate fungal interactions and enhance secondary metabolite production. Promising extracts were fractionated, yielding compounds such as the iron complex of fusaric acid (\n                    <jats:bold>1<\/jats:bold>\n                    ), magnesium complex of fusaric acid (\n                    <jats:bold>2<\/jats:bold>\n                    ), haematocin (\n                    <jats:bold>4<\/jats:bold>\n                    ), fusarinolic acid (\n                    <jats:bold>7<\/jats:bold>\n                    ), and cyclonerodiol (\n                    <jats:bold>8<\/jats:bold>\n                    ). These compounds exhibited significant papain inhibitory activity, with compounds\n                    <jats:bold>2<\/jats:bold>\n                    and\n                    <jats:bold>4<\/jats:bold>\n                    showing IC\n                    <jats:sub>50<\/jats:sub>\n                    values below 20\u00a0\u00b5M. Notable anti\u2010\n                    <jats:italic>Trypanosoma cruzi<\/jats:italic>\n                    activity was also observed, particularly for compounds\n                    <jats:bold>2<\/jats:bold>\n                    (50% inhibitory concentration [IC\n                    <jats:sub>50<\/jats:sub>\n                    ] = 12.19\u00a0\u00b5M) and\n                    <jats:bold>4<\/jats:bold>\n                    (IC\n                    <jats:sub>50<\/jats:sub>\n                    = 13.32\u00a0\u00b5M). Additionally, antifungal activity against\n                    <jats:italic>Candida<\/jats:italic>\n                    spp. was detected, with compound\n                    <jats:bold>2<\/jats:bold>\n                    and the magnesium complex of 9,10\u2010dehydrofusaric acid complex (\n                    <jats:bold>3<\/jats:bold>\n                    ) showing MICs of 50\u00a0\u00b5g\/mL. This study highlights the potential of fungal co\u2010cultivation and variation in culture medium as effective strategies for discovering novel bioactive protease inhibitors and antiparasitic agents.\n                  <\/jats:p>","DOI":"10.1002\/cbdv.202501135","type":"journal-article","created":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T19:51:49Z","timestamp":1756842709000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Co\u2010cultivation and Medium Optimization: A Strategy for Discovering Fungal\u2010derived Protease Inhibitors"],"prefix":"10.1002","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9859-8551","authenticated-orcid":false,"given":"Vitor de Souza","family":"Mazucato","sequence":"first","affiliation":[{"name":"Department of BioMolecular Sciences, Ribeir\u00e3o Preto School of Pharmaceutical Sciences University of S\u00e3o Paulo  Ribeirao Preto 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