{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T20:36:14Z","timestamp":1769200574102,"version":"3.49.0"},"reference-count":55,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2018,2,5]],"date-time":"2018-02-05T00:00:00Z","timestamp":1517788800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>NAD+-dependent histone deacetylases (sirtuins) are implicated in cellular processes such as proliferation, DNA repair, and apoptosis by regulating gene expression and the functions of numerous proteins. Due to their key role in cells, the discovery of small molecule sirtuin modulators has been of significant interest for diverse therapeutic applications. In particular, it has been shown that inhibition of sirtuin 1 and 2 activities is beneficial for cancer treatment. Here, we demonstrate that the fungal metabolite eurochevalierine from the fungus Neosartorya pseudofischeri inhibits sirtuin 1 and 2 activities (IC50 about 10 \u00b5M) without affecting sirtuin 3 activity. The binding modes of the eurochevalierine for sirtuin 1 and 2 have been identified through computational docking analyses. Accordingly, this sequiterpene alkaloid induces histone H4 and \u03b1-tubulin acetylation in various cancer cell models in which it induces strong cytostatic effects without affecting significantly the viability of healthy PBMCs. Importantly, eurochevalierine targets preferentially cancer cell proliferation (selectivity factor \u226b 7), as normal human primary CD34+ stem\/progenitor cells were less affected by the treatment. Finally, eurochevalierine displays suitable drug-likeness parameters and therefore represent a promising scaffold for lead molecule optimization to study the mechanism and biological roles of sirtuins and potentially a basis for development into therapeutics.<\/jats:p>","DOI":"10.3390\/molecules23020333","type":"journal-article","created":{"date-parts":[[2018,2,5]],"date-time":"2018-02-05T10:12:49Z","timestamp":1517825569000},"page":"333","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["The Fungal Metabolite Eurochevalierine, a Sequiterpene Alkaloid, Displays Anti-Cancer Properties through Selective Sirtuin 1\/2 Inhibition"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0550-9538","authenticated-orcid":false,"given":"Michael","family":"Schnekenburger","sequence":"first","affiliation":[{"name":"Laboratoire de Biologie Mol\u00e9culaire et Cellulaire du Cancer, H\u00f4pital Kirchberg, 9, rue Edward Steichen, L-2540 Luxembourg, Luxembourg"}]},{"given":"V\u00e9ronique","family":"Mathieu","sequence":"additional","affiliation":[{"name":"Department of Pharmacotherapy and Pharmaceutics, Facult\u00e9 de Pharmacie, Universit\u00e9 Libre de Bruxelles, Boulevard du Triomphe, 1050 Brussels, Belgium"}]},{"given":"Florence","family":"Lefranc","sequence":"additional","affiliation":[{"name":"Service de Neurochirurgie, H\u00f4pital Erasme, Universit\u00e9 Libre de Bruxelles, 808 Route de Lennik, 1070 Brussels, Belgium"}]},{"given":"Jun Young","family":"Jang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, 1 Gwanak-ro Gwanak-gu, Seoul 08826, Korea"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0609-8902","authenticated-orcid":false,"given":"Marco","family":"Masi","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Chimiche, Universit\u00e0 di Napoli Federico II, Via Cintia 4, 80126 Napoli, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3321-1061","authenticated-orcid":false,"given":"Anake","family":"Kijjoa","sequence":"additional","affiliation":[{"name":"Instituto de Ci\u00eancias Biom\u00e9dicas de Abel Salazar (ICBAS) and CIIMAR, Universidade do Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal"}]},{"given":"Antonio","family":"Evidente","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Chimiche, Universit\u00e0 di Napoli Federico II, Via Cintia 4, 80126 Napoli, Italy"}]},{"given":"Hyun-Jung","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Chung-Ang University, 84 Heukseok-ro Dongjak-gu, Seoul 06974, Korea"}]},{"given":"Robert","family":"Kiss","sequence":"additional","affiliation":[{"name":"Retired \u2013 previously Director of Research at the Fonds National de la Recherche Scientifique (FRS-FNRS; Belgium)"}]},{"given":"Mario","family":"Dicato","sequence":"additional","affiliation":[{"name":"Laboratoire de Biologie Mol\u00e9culaire et Cellulaire du Cancer, H\u00f4pital Kirchberg, 9, rue Edward Steichen, L-2540 Luxembourg, Luxembourg"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7571-3791","authenticated-orcid":false,"given":"Byung Woo","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, 1 Gwanak-ro Gwanak-gu, Seoul 08826, Korea"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0115-4725","authenticated-orcid":false,"given":"Marc","family":"Diederich","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, 1 Gwanak-ro Gwanak-gu, Seoul 08826, Korea"}]}],"member":"1968","published-online":{"date-parts":[[2018,2,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1650","DOI":"10.1093\/annonc\/mdu138","article-title":"European cancer mortality predictions for the year 2014","volume":"25","author":"Malvezzi","year":"2014","journal-title":"Ann. 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