{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T18:56:04Z","timestamp":1769972164039,"version":"3.49.0"},"reference-count":47,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T00:00:00Z","timestamp":1769731200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004704","name":"National Research Council of Thailand","doi-asserted-by":"crossref","award":["N41A640345"],"award-info":[{"award-number":["N41A640345"]}],"id":[{"id":"10.13039\/501100004704","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"crossref","award":["CZ.02.1.01\/0.0\/0.0\/16_019\/0000868"],"award-info":[{"award-number":["CZ.02.1.01\/0.0\/0.0\/16_019\/0000868"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Czech Agency","award":["23-05474S"],"award-info":[{"award-number":["23-05474S"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JoF"],"abstract":"<jats:p>The extract of Xylaria thienhirunae SWUF17-44.1 displayed broad-spectrum antimicrobial activity, with higher potency against Gram-positive bacteria than Gram-negative strains. Minimum inhibitory concentration (MIC) values were as low as 0.63 \u00b5g\/\u00b5L for Staphylococcus aureus and 1.25 \u00b5g\/\u00b5L for Bacillus subtilis, whereas higher values were observed for Escherichia coli and Pseudomonas aeruginosa. The extract also inhibited fungal growth, with MICs of 6.25 \u03bcg\/\u03bcL against Candida albicans and C. tropicalis. Strong antioxidant activity was observed (DPPH IC50 = 0.706 \u00b1 0.022 \u03bcg\/\u03bcL; ABTS IC50 = 0.251 \u00b1 0.019 \u03bcg\/\u03bcL), correlated with high phenolic content. Moderate anti-inflammatory activity was confirmed via nitric oxide inhibition. LC-MS profiling indicated diverse metabolites, including phenolic derivatives, aminoglycoside-like compounds, and annotated bioactive molecules. Chromatographic isolation yielded four compounds: 4-(2,3-dihydroxypropoxy)benzoic acid, 4-prenyloxybenzoic acid, and two novel metabolites, xylerithienol and xylerithiether. In silico docking predicted strong interactions of the novel compounds with bacterial targets such as muramyl ligases, DNA gyrase B, and \u03b2-ketoacyl-ACP synthase III. Notably, xylerithiether outperformed norfloxacin against DNA gyrase B and fluconazole against sterol 14-\u03b1-demethylase. In vitro antibacterial activity was assessed for the purified compounds; all were active, predominantly against Gram-positive bacteria. These finding position X. thienhirunae SWUF17-44.1 as a promising source of bioactive metabolites and potential scaffolds for antimicrobial drug discovery.<\/jats:p>","DOI":"10.3390\/jof12020093","type":"journal-article","created":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T13:04:46Z","timestamp":1769778286000},"page":"93","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Novel Metabolites of Xylaria\u00a0thienhirunae SWUF17-44.1 with Biological Activities and Molecular Docking Analysis"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-5717-5003","authenticated-orcid":false,"given":"Pitchapa","family":"Thongsuwan","sequence":"first","affiliation":[{"name":"Department of Microbiology, Faculty of Science, Srinakharinwirot University, 114 Sukhumvit 23, Wattana, Bangkok 10110, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1157-2405","authenticated-orcid":false,"given":"Lutfun","family":"Nahar","sequence":"additional","affiliation":[{"name":"Centre for Natural Products Discovery, School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Byrom Street, Liverpool L3 3AF, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4038-0514","authenticated-orcid":false,"given":"Satyajit D.","family":"Sarker","sequence":"additional","affiliation":[{"name":"Centre for Natural Products Discovery, School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Byrom Street, Liverpool L3 3AF, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-8001-5436","authenticated-orcid":false,"given":"Pitchaya","family":"Kongmaung","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Science, Srinakharinwirot University, 114 Sukhumvit 23, Wattana, Bangkok 10110, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2421-7859","authenticated-orcid":false,"given":"Kiattawee","family":"Choowongkomon","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Science, Kasetsart University, Bangkok 10900, Thailand"},{"name":"Center for Advanced Studies in Nanotechnology for Chemical, Food and Agricultural Industries, KU Institute for Advanced Studies, Kasetsart University, Bangkok 10900, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3963-752X","authenticated-orcid":false,"given":"Cherdchai","family":"Phosri","sequence":"additional","affiliation":[{"name":"Department of Biology, Faculty of Science, Nakhon Phanom University, Nakhon Phanom 48000, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0599-5732","authenticated-orcid":false,"given":"Nuttika","family":"Suwannasai","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Science, Srinakharinwirot University, 114 Sukhumvit 23, Wattana, Bangkok 10110, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/s40529-023-00389-6","article-title":"Exploring the Xylariaceae and its relatives","volume":"64","author":"Suwannasai","year":"2023","journal-title":"Bot. Stud."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Chen, W., Yu, M., Chen, S., Gong, T., Xie, L., Liu, J., Bian, C., Huang, G., and Zheng, C. (2024). Structures and biological activities of secondary metabolites from Xylaria spp.. J. Fungi., 10.","DOI":"10.3390\/jof10030190"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"100118","DOI":"10.1016\/j.simyco.2021.100118","article-title":"Secondary metabolite biosynthetic diversity in the fungal family Hypoxylaceae and Xylaria hypoxylon","volume":"99","author":"Kuhnert","year":"2021","journal-title":"Stud. Mycol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1007\/s13659-023-00427-7","article-title":"Antiproliferative polyketides from fungus Xylaria cf. Longipes SWUF08-81 in different culture media","volume":"14","author":"Sresuksai","year":"2024","journal-title":"Nat. Prod. Bioprospect."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"120041","DOI":"10.1016\/j.jep.2025.120041","article-title":"A comprehensive review of the metabolites, biological activities, and clinical application of a medicinal fungus Xylaria nigripes","volume":"350","author":"Liang","year":"2025","journal-title":"J. Ethnopharmacol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.jff.2017.05.027","article-title":"In vitro and in vivo assessment of anti-inflammatory and immunomodulatory activities of Xylaria nigripes mycelium","volume":"35","author":"Divate","year":"2017","journal-title":"J. Funct. Foods"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1021\/acs.jnatprod.2c00881","article-title":"Eremoxylarins D\u2013J, antibacterial eremophilane sesquiterpenes discovered from an endolichenic strain of Xylaria hypoxylon","volume":"86","author":"Miral","year":"2023","journal-title":"J. Nat. Prod."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"5285","DOI":"10.1016\/j.tet.2015.06.020","article-title":"Xylapyrrosides A and B, two rare sugar-morpholine spiroketal pyrrole-derived alkaloids from Xylaria nigripes: Isolation, complete structure elucidation, and total syntheses","volume":"71","author":"Li","year":"2015","journal-title":"Tetrahedron"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Zhang, X., Fan, Y., Ye, K., Pan, X., Ma, X., Ai, H., Shi, B., and Liu, J. (2023). Six unprecedented cytochalasin derivatives from the potato endophytic fungus Xylaria curta E10 and their cytotoxicity. Pharmaceuticals, 16.","DOI":"10.3390\/ph16020193"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1038\/d41586-024-03033-w","article-title":"40 million deaths by 2050: Toll of drug-resistant infections to rise by 70%","volume":"633","author":"Naddaf","year":"2024","journal-title":"Nature"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1111\/mmi.12758","article-title":"The biology of Mur ligases as an antibacterial target","volume":"94","author":"Kouidmi","year":"2014","journal-title":"Mol. Microbiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"143325","DOI":"10.1016\/j.ijbiomac.2025.143325","article-title":"Mapping dihydropteroate synthase evolvability through identification of a novel evolutionarily critical substructure","volume":"311","author":"Sanyal","year":"2025","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e00273","DOI":"10.1128\/mBio.00273-13","article-title":"Clinically relevant mutant DNA gyrase alters supercoiling, changes the transcriptome, and confers multidrug resistance","volume":"4","author":"Webber","year":"2013","journal-title":"mBio"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"6717","DOI":"10.1007\/s11696-023-02971-5","article-title":"Identification of potential DNA gyrase inhibitors: Virtual screening, extra-precision docking and molecular dynamics simulation study","volume":"77","author":"Kumar","year":"2023","journal-title":"Chem. Pap."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"117995","DOI":"10.1016\/j.ejmech.2025.117995","article-title":"Recent Developments of the \u03b2-ketoacyl-acyl carrier protein synthase III (FabH) Inhibitors: Emerging Indication as Antibacterial Agents","volume":"298","author":"Verma","year":"2025","journal-title":"Eur. J. Med. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/S0065-2911(03)47003-3","article-title":"The biodiversity of microbial cytochromes P450","volume":"47","author":"Kelly","year":"2003","journal-title":"Adv. Microb. Physiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e202301276","DOI":"10.1002\/cbdv.202301276","article-title":"Anticandidal Effect of New Imidazole Derivatives Over Aspartic Protease Inhibition","volume":"21","author":"Jeevitha","year":"2024","journal-title":"Chem. Biodivers."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1039\/C9CB00017H","article-title":"A mechanism-inspired UDP-N-acetylglucosamine pyrophosphorylase inhibitor","volume":"1","author":"Raimi","year":"2020","journal-title":"RSC Chem. Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/s40199-015-0106-9","article-title":"Molecular docking and inhibition studies on the interactions of Bacopa monnieri\u2019s potent phytochemicals against pathogenic Staphylococcus aureus","volume":"23","author":"Emran","year":"2015","journal-title":"DARU J. Pharm. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"146","DOI":"10.2174\/157340911795677602","article-title":"Molecular docking: A powerful approach for structure-based drug discovery","volume":"7","author":"Meng","year":"2011","journal-title":"Curr. Comput. Aided Drug Des."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Wangsawat, N., Ju, Y.-M., Phosri, C., Whalley, A.J., and Suwannasai, N. (2021). Twelve new taxa of Xylaria associated with termite nests and soil from northeast Thailand. Biology, 10.","DOI":"10.3390\/biology10070575"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Wangsawat, N., Nahar, L., Sarker, S.D., Phosri, C., Evans, A.R., Whalley, A.J., Choowongkomon, K., and Suwannasai, N. (2021). Antioxidant activity and cytotoxicity against cancer cell lines of the extracts from novel Xylaria species associated with termite nests and LC-MS analysis. Antioxidants, 10.","DOI":"10.3390\/antiox10101557"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/j.ymeth.2007.01.006","article-title":"Microtitre plate-based antibacterial assay incorporating resazurin as an indicator of cell growth, and its application in the in vitro antibacterial screening of phytochemicals","volume":"42","author":"Sarker","year":"2007","journal-title":"Methods"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e41446","DOI":"10.5812\/jjm.41446","article-title":"The frequency, antifungal susceptibility and enzymatic profiles of Candida species isolated from neutropenic patients","volume":"9","author":"Gharaghani","year":"2016","journal-title":"Jundishapur J. Microbiol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Staniszewska, M., Kuryk, \u0141., Gryciuk, A., Kawalec, J., Rogalska, M., Baran, J., \u0141ukowska-Chojnacka, E., and Kowalkowska, A. (2021). In vitro anti-candida activity and action mode of benzoxazole derivatives. Molecules, 26.","DOI":"10.3390\/molecules26165008"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Rusu, M.E., Gheldiu, A.-M., Mocan, A., Moldovan, C., Popa, D.-S., Tomuta, I., and Vlase, L. (2018). Process optimization for improved phenolic compounds recovery from walnut (Juglans regia L.) septum: Phytochemical profile and biological activities. Molecules, 23.","DOI":"10.3390\/molecules23112814"},{"key":"ref_27","first-page":"58","article-title":"Evaluation of Biological Activities and Cytotoxicity of Microporus vernicipes PW17-173 and Microporus xanthopus PP17-16 Mushroom Extracts for Natural Cosmetics Applications","volume":"40","author":"Karin","year":"2024","journal-title":"Sci. Ess. J."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Cole, J., Nissink, J.W.M., and Taylor, R. (2005). Protein-Ligand Docking and Virtual Screening with GOLD, Taylor & Francis CRC Press.","DOI":"10.1201\/9781420028775.ch15"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1096\/fj.07-8506com","article-title":"Acetaminophen (paracetamol) is a selective cyclooxygenase-2 inhibitor in man","volume":"22","author":"Hinz","year":"2008","journal-title":"FASEB J."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1016\/j.jscs.2014.12.004","article-title":"Synthesis, antimicrobial and antitubercular activities of some novel pyrazoline derivatives","volume":"20","author":"Ahmad","year":"2016","journal-title":"J. Saudi Chem. Soc."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/0008-6215(82)84029-9","article-title":"Isolation and structures of istamycin components","volume":"109","author":"Ikeda","year":"1982","journal-title":"Carbohydr. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1128\/AAC.10.5.827","article-title":"Biological activity of netilmicin, a broad-spectrum semisynthetic aminoglycoside antibiotic","volume":"10","author":"Miller","year":"1976","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1055\/s-2007-971406","article-title":"Kolanone, a novel polyisoprenylated benzophenone with antimicrobial properties from the fruit of Garcinia kola","volume":"44","author":"Hussain","year":"1982","journal-title":"Planta Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1021\/np50079a022","article-title":"Westiellamide, a bistratamide-related cyclic peptide from the blue-green alga Westiellopsis prolifica","volume":"55","author":"Prinsep","year":"1992","journal-title":"J. Nat. Prod."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"133479","DOI":"10.1016\/j.molstruc.2022.133479","article-title":"Thiazole derivatives in medicinal chemistry: Recent advancements in synthetic strategies, structure activity relationship and pharmacological outcomes","volume":"1266","author":"Singh","year":"2022","journal-title":"J. Mol. Struct."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1016\/j.procbio.2020.01.028","article-title":"Bioactivity-guided isolation of antimicrobial metabolite from Xylaria sp.","volume":"92","author":"Rakshith","year":"2020","journal-title":"Process Biochem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.hjb.2016.06.005","article-title":"Antibacterial activity of extracellular protease isolated from an algicolous fungus Xylaria psidii KT30 against gram-positive bacteria","volume":"23","author":"Indarmawan","year":"2016","journal-title":"HAYATI J. Biosci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1016\/j.bjm.2018.03.003","article-title":"The potential of compounds isolated from Xylaria spp. as antifungal agents against anthracnose","volume":"49","author":"Elias","year":"2018","journal-title":"Braz. J. Microbiol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Pham, N.S., Le, T.T.X., Pham, Q.A., Vu, T.H.N., Quach, N.T., Nguyen, T.T.L., Do, T.T., Do, H.A., Tran, H.Q., and Chu, K.-S. (2024). The Cytotoxicity and Antioxidant Potentials of the Endophytic Fungus Xylaria sp. KET18 Associated with Keteleeria evelyniana Mast. Appl. Sci., 14.","DOI":"10.3390\/app142311070"},{"key":"ref_40","first-page":"154","article-title":"Steroids and dihydroisocoumarin glycosides from Xylaria sp. by the one strain many compounds strategy and their bioactivities","volume":"21","author":"Dong","year":"2023","journal-title":"Chin. J. Nat. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2010","DOI":"10.1080\/14786419.2019.1652292","article-title":"Anti-inflammatory and cytotoxic agents from Xylaria sp. SWUF09-62 fungus","volume":"35","author":"Patjana","year":"2021","journal-title":"Nat. Prod. Res."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Kong, J., Wu, Z.-X., Wei, L., Chen, Z.-S., and Yoganathan, S. (2020). Exploration of antibiotic activity of aminoglycosides, in particular ribostamycin alone and in combination with ethylenediaminetetraacetic acid against pathogenic bacteria. Front. Microbiol., 11.","DOI":"10.3389\/fmicb.2020.01718"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"114011","DOI":"10.1016\/j.phytochem.2024.114011","article-title":"Sesquiterpenes and \u03b1-pyrones from an endophytic fungus Xylaria curta YSJ-5","volume":"220","author":"Wei","year":"2024","journal-title":"Phytochemistry"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.procbio.2021.10.010","article-title":"Antibacterial activity of ethyl acetate extract of endophytic fungus (Paraconiothyrium brasiliense) through targeting dihydropteroate synthase (DHPS)","volume":"111","author":"Sathiyaseelan","year":"2021","journal-title":"Process Biochem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1007\/s00203-025-04429-6","article-title":"DNA gyrase-inhibitory antimicrobial anthraquinone from the endophytic Sordariomycetes fungus Diaporthe perseae","volume":"207","author":"Manzano","year":"2025","journal-title":"Arch. Microbiol."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Leaver, D.J. (2018). Synthesis and biological activity of sterol 14\u03b1-demethylase and sterol C24-methyltransferase inhibitors. Molecules, 23.","DOI":"10.3390\/molecules23071753"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Bras, G., Satala, D., Juszczak, M., Kulig, K., Wronowska, E., Bednarek, A., Zawrotniak, M., Rapala-Kozik, M., and Karkowska-Kuleta, J. (2024). Secreted aspartic proteinases: Key factors in Candida infections and host-pathogen interactions. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25094775"}],"container-title":["Journal of Fungi"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2309-608X\/12\/2\/93\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T05:12:42Z","timestamp":1769922762000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2309-608X\/12\/2\/93"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,30]]},"references-count":47,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["jof12020093"],"URL":"https:\/\/doi.org\/10.3390\/jof12020093","relation":{},"ISSN":["2309-608X"],"issn-type":[{"value":"2309-608X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,30]]}}}