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Mass drug administration is currently the most important control measure, but the use of the few available drugs is giving rise to increased resistance of the parasites to the drugs. Different approaches are needed to come up with new therapeutic agents against these helminths. Fungi are a source of secondary metabolites, but most fungi remain largely uninvestigated as anthelmintics. In this report, the anthelmintic activity of Albatrellus confluens against Caenorhabditis elegans was investigated using bio-assay guided isolation. Grifolin (1) and neogrifolin (2) were identified as responsible for the anthelmintic activity. Derivatives 4\u20136 were synthesized to investigate the effect of varying the prenyl chain length on anthelmintic activity. The isolated compounds 1 and 2 and synthetic derivatives 4\u20136, as well as their educts 7\u201310, were tested against Schistosoma mansoni (adult and newly transformed schistosomula), Strongyloides ratti, Heligmosomoides polygyrus, Necator americanus, and Ancylostoma ceylanicum. Prenyl-2-orcinol (4) and geranylgeranyl-2-orcinol (6) showed promising activity against newly transformed schistosomula. The compounds 1, 2, 4, 5, and 6 were also screened for antiproliferative or cytotoxic activity against two human cancer lines, viz. prostate adenocarcinoma cells (PC-3) and colorectal adenocarcinoma cells (HT-29). Compound 6 was determined to be the most effective against both cell lines with IC50 values of 16.1 \u00b5M in PC-3 prostate cells and 33.7 \u00b5M in HT-29 colorectal cells.<\/jats:p>","DOI":"10.3390\/molecules27092950","type":"journal-article","created":{"date-parts":[[2022,5,6]],"date-time":"2022-05-06T02:46:39Z","timestamp":1651805199000},"page":"2950","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Albatrellus confluens (Alb. &amp; Schwein.) Kotl. &amp; Pouz.: Natural Fungal Compounds and Synthetic Derivatives with In Vitro Anthelmintic Activities and Antiproliferative Effects against Two Human Cancer Cell Lines"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1043-0480","authenticated-orcid":false,"given":"Mthandazo","family":"Dube","sequence":"first","affiliation":[{"name":"Department of Bioorganic Chemistry, Leibniz Institute of Plant Biochemistry, Weinberg 3, D-06120 Halle (Saale), Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dayma","family":"Llanes","sequence":"additional","affiliation":[{"name":"Department of Bioorganic Chemistry, Leibniz Institute of Plant Biochemistry, Weinberg 3, D-06120 Halle (Saale), Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0749-8692","authenticated-orcid":false,"given":"Mohamad","family":"Saoud","sequence":"additional","affiliation":[{"name":"Department of Bioorganic Chemistry, Leibniz Institute of Plant Biochemistry, Weinberg 3, D-06120 Halle (Saale), Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Rennert","sequence":"additional","affiliation":[{"name":"Department of Bioorganic Chemistry, Leibniz Institute of Plant Biochemistry, Weinberg 3, D-06120 Halle (Saale), Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Imming","sequence":"additional","affiliation":[{"name":"Institute of Pharmacy, Faculty of Natural Sciences, Martin-Luther-University Halle-Wittenberg, D-06120 Halle (Saale), Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C\u00e9cile","family":"H\u00e4berli","sequence":"additional","affiliation":[{"name":"Swiss Tropical and Public Health Institute, Kreuzstrasse 2, CH-4123 Allschwil, Switzerland"},{"name":"University of Basel, CH-4051 Basel, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0290-3521","authenticated-orcid":false,"given":"Jennifer","family":"Keiser","sequence":"additional","affiliation":[{"name":"Swiss Tropical and Public Health Institute, Kreuzstrasse 2, CH-4123 Allschwil, Switzerland"},{"name":"University of Basel, CH-4051 Basel, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Norbert","family":"Arnold","sequence":"additional","affiliation":[{"name":"Department of Bioorganic Chemistry, Leibniz Institute of Plant Biochemistry, Weinberg 3, D-06120 Halle (Saale), Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/bs.apar.2018.08.002","article-title":"Drug combinations against soil transmitted helminth infections","volume":"103","author":"Moser","year":"2019","journal-title":"Adv. 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