{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T15:01:16Z","timestamp":1772118076700,"version":"3.50.1"},"reference-count":32,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T00:00:00Z","timestamp":1696982400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Archiv der Pharmazie"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Natural products belonging to different chemical classes have been established as a promising source of novel anticancer drugs. Several low\u2010molecular\u2010weight compounds from the classes of monoterpenes, phenylpropanoids, and flavonoids were shown to possess anticancer activities in previous studies. In this work, over 20 semisynthetic derivatives of molecules belonging to these classes, namely thymol, eugenol, and 6\u2010hydroxyflavanone were synthesized and tested for their cytotoxicity against two human cancer cell lines, namely AGS cells (gastric adenocarcinoma) and A549 cells (human lung carcinoma). An initial screening based on viability assessment was performed to identify the most cytotoxic compounds at 100\u2009\u03bcM. The results evidenced that two 6\u2010hydroxyflavanone derivatives were the most cytotoxic among the compounds tested, being selected for further studies. These derivatives displayed enhanced toxicity when compared with their natural counterparts. Moreover, the lactate dehydrogenase (LDH) assay showed that the loss of cell viability was not accompanied by a loss of membrane integrity, thus ruling out a necrotic process. Morphological studies with AGS cells demonstrated chromatin condensation compatible with apoptosis, confirmed by the activation of caspase 3\/7. Furthermore, a viability assay on a noncancer human embryonic lung fibroblast cell line (MRC\u20105) confirmed that these two derivatives possess selective anticancer activity.<\/jats:p>","DOI":"10.1002\/ardp.202300294","type":"journal-article","created":{"date-parts":[[2023,10,12]],"date-time":"2023-10-12T02:09:00Z","timestamp":1697076540000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Structural modification of naturally occurring phenolics as a strategy for developing cytotoxic molecules towards cancer cells"],"prefix":"10.1002","volume":"356","author":[{"given":"Pedro","family":"Olim","sequence":"first","affiliation":[{"name":"REQUIMTE\/LAQV, Laboratory of Pharmacognosy, Department of Chemistry, Faculty of Pharmacy University of Porto  Porto Portugal"}]},{"given":"Renato B.","family":"Pereira","sequence":"additional","affiliation":[{"name":"REQUIMTE\/LAQV, Laboratory of Pharmacognosy, Department of Chemistry, Faculty of Pharmacy University of Porto  Porto Portugal"}]},{"given":"Maria Jos\u00e9 G.","family":"Fernandes","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Centre of Chemistry (CQUM) University of Minho  Campus of Gualtar Braga Portugal"}]},{"given":"Carolina M.","family":"Natal","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Centre of Chemistry (CQUM) University of Minho  Campus of Gualtar Braga Portugal"}]},{"given":"Jos\u00e9 R. A.","family":"Coelho","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Centre of Chemistry (CQUM) University of Minho  Campus of Gualtar Braga Portugal"}]},{"given":"A. Gil","family":"Fortes","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Centre of Chemistry (CQUM) University of Minho  Campus of Gualtar Braga Portugal"}]},{"given":"M. Sameiro T.","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Centre of Chemistry (CQUM) University of Minho  Campus of Gualtar Braga Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0384-7592","authenticated-orcid":false,"given":"David M.","family":"Pereira","sequence":"additional","affiliation":[{"name":"REQUIMTE\/LAQV, Laboratory of Pharmacognosy, Department of Chemistry, Faculty of Pharmacy University of Porto  Porto Portugal"}]}],"member":"311","published-online":{"date-parts":[[2023,10,11]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jnatprod.5b01055"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-020-00114-z"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1168243"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fpls.2019.00943"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1177\/1934578X0800300801"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-018-0121-1"},{"key":"e_1_2_7_8_1","first-page":"1","volume-title":"Natural Products Targeting Clinically Relevant Enzymes","author":"Pereira D. 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