{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T21:00:59Z","timestamp":1792270859594,"version":"4.4.0"},"reference-count":41,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,6,14]],"date-time":"2021-06-14T00:00:00Z","timestamp":1623628800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Economic Development and Innovation Operative Programme","award":["GINOP-2.3.2-15-2016-00012, GINOP-2.3.2-15-2016-00015 and GINOP-2.3.2-15-2016-00032"],"award-info":[{"award-number":["GINOP-2.3.2-15-2016-00012, GINOP-2.3.2-15-2016-00015 and GINOP-2.3.2-15-2016-00032"]}]},{"name":"New National Excellence Program of the Ministry for Innovation and Technology from the source of the National Research, Development and Innovation Funds","award":["\u00daNKP-20-4"],"award-info":[{"award-number":["\u00daNKP-20-4"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Plants"],"abstract":"<jats:p>Ingenol mebutate, isolated from Euphorbia peplus, is an ingenane-type diterpenoid, primarily used for the topical treatment of actinic keratosis, a premalignant skin condition. The aim of our work was to investigate other Euphorbia species to find structurally similar diterpenes that can be used as alternatives to ingenol mebutate. Pharmacological investigation of Euphorbia candelabrum, Euphorbia cotinifolia, Euphorbia ramipressa, and Euphorbia trigona revealed the potent keratinocyte (HPV-Ker cell line) inhibitory activity of these spurge species. From the methanolic extract of the aerial parts of Euphorbia trigona Miller, the most active species, five ingol (1\u20135) and four ingenane-type diterpenoids (6\u20139) were isolated by various chromatographic separation techniques, including open column chromatography, vacuum liquid chromatography, thin-layer chromatography, and high-performance liquid chromatography. The structures of the compounds were determined by NMR spectroscopic analysis and by comparison of the assignations with the literature data. The cytotoxic activity of the compounds against keratinocytes was tested in vitro by using ingenol mebutate as a positive control. Among the isolated compounds, two ingenane derivatives (6 and 7) exhibited remarkably stronger cytotoxic activity (IC50 values 0.39 \u03bcM and 0.32 \u03bcM, respectively) on keratinocytes than ingenol mebutate (IC50 value 0.84 \u03bcM). These compounds could serve as starting materials for further investigations to find alternatives to Picato\u00ae (with active substance ingenol mebutate), which was withdrawn from marketing authorization in the European Union.<\/jats:p>","DOI":"10.3390\/plants10061206","type":"journal-article","created":{"date-parts":[[2021,6,14]],"date-time":"2021-06-14T22:25:46Z","timestamp":1623709546000},"page":"1206","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Ingol and Ingenol-Type Diterpenes from Euphorbia trigona Miller with Keratinocyte Inhibitory Activity"],"prefix":"10.3390","volume":"10","author":[{"given":"Reham","family":"Hammadi","sequence":"first","affiliation":[{"name":"Department of Pharmacognosy, Interdisciplinary Excellence Centre, University of Szeged, E\u00f6tv\u00f6s u. 6, 6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9973-6442","authenticated-orcid":false,"given":"Norbert","family":"K\u00fasz","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, Interdisciplinary Excellence Centre, University of Szeged, E\u00f6tv\u00f6s u. 6, 6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Csilla Zsuzsanna","family":"D\u00e1vid","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, Interdisciplinary Excellence Centre, University of Szeged, E\u00f6tv\u00f6s u. 6, 6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zolt\u00e1n","family":"Beh\u00e1ny","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Allergology, University of Szeged, Kor\u00e1nyi fasor 6, 6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00e1szl\u00f3","family":"Papp","sequence":"additional","affiliation":[{"name":"Botanical Garden, E\u00f6tv\u00f6s Lor\u00e1nd University, Ill\u00e9s u. 25, 1083 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2119-9501","authenticated-orcid":false,"given":"Lajos","family":"Kem\u00e9ny","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Allergology, University of Szeged, Kor\u00e1nyi fasor 6, 6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judit","family":"Hohmann","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, Interdisciplinary Excellence Centre, University of Szeged, E\u00f6tv\u00f6s u. 6, 6720 Szeged, Hungary"},{"name":"Interdisciplinary Centre of Natural Products, University of Szeged, E\u00f6tv\u00f6s u. 6, 6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00f3r\u00e1nt","family":"Lakatos","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Allergology, University of Szeged, Kor\u00e1nyi fasor 6, 6720 Szeged, Hungary"},{"name":"Photo- and Chronobiology Group E\u00f6tv\u00f6s Lor\u00e1nd Research Network (ELKH), Institute of Plant Biology, Biological Research Center Szeged, Temesv\u00e1ri krt. 62, 6726 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1818-7702","authenticated-orcid":false,"given":"Andrea","family":"Vasas","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, Interdisciplinary Excellence Centre, University of Szeged, E\u00f6tv\u00f6s u. 6, 6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1111\/ijd.14147","article-title":"Actinic keratosis\u2014Review for clinical practice","volume":"58","author":"Pantoja","year":"2019","journal-title":"Int. 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