{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T21:26:06Z","timestamp":1776115566076,"version":"3.50.1"},"reference-count":31,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2021,8,5]],"date-time":"2021-08-05T00:00:00Z","timestamp":1628121600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009687","name":"Uniwersytet Medyczny im. Piast\u00f3w Slaskich we Wroclawiu","doi-asserted-by":"publisher","award":["STM.A050.20.032"],"award-info":[{"award-number":["STM.A050.20.032"]}],"id":[{"id":"10.13039\/501100009687","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009687","name":"Uniwersytet Medyczny im. Piast\u00f3w Slaskich we Wroclawiu","doi-asserted-by":"publisher","award":["SUB.A400.21.040"],"award-info":[{"award-number":["SUB.A400.21.040"]}],"id":[{"id":"10.13039\/501100009687","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Phenolic acids possess many beneficial biological activities, including antioxidant and anti-inflammatory properties. Unfortunately, their low bioavailability restricts their potential medical uses, as it limits the concentration of phenolic acids achievable in the organism. The conjugation with phospholipids constitutes one of the most effective strategies to enhance compounds bioavailability in biological systems. In the present study, the conjugates of anisic (ANISA) and veratric acid (VA) with phosphatidylcholine (PC) were investigated. Since both ANISA and VA are inhibitors of tyrosinase, a melanocyte enzyme, the expression of which increases during tumorigenesis, anticancer potential of the conjugates was tested in several metastatic melanoma cell lines. The conjugates proved to be antiproliferative, apoptosis-inducing and cell-cycle-affecting agents, selective for cancerous cells and not affecting normal fibroblasts. The conjugates substituted by ANISA and VA, respectively, at both the sn-1 and sn-2 positions of PC, appeared the most promising, since they were effective against the vast majority of metastatic melanoma cell lines. Additionally, the conjugation of phenolic acids to PC increased their antioxidant activity. Molecular modeling was employed for the first time to estimate the features of the investigated conjugates relevant to their anticancer properties and membrane permeation. Again, the conjugates substituted by phenolic acid at both the sn-1 and sn-2 positions of PC seemed to be presumably most bioavailable.<\/jats:p>","DOI":"10.3390\/ijms22168397","type":"journal-article","created":{"date-parts":[[2021,8,5]],"date-time":"2021-08-05T04:33:29Z","timestamp":1628138009000},"page":"8397","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Conjugation with Phospholipids as a Modification Increasing Anticancer Activity of Phenolic Acids in Metastatic Melanoma\u2014In Vitro and In Silico Studies"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4246-5717","authenticated-orcid":false,"given":"Anna","family":"Palko-\u0141abuz","sequence":"first","affiliation":[{"name":"Department of Biophysics and Neuroscience, Wroclaw Medical University, ul. Chalubinskiego 3a, 50-368 Wroclaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0218-6369","authenticated-orcid":false,"given":"Anna","family":"Gliszczy\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Wroc\u0142aw University of Environmental and Life Sciences, Norwida 25, 50-375 Wroc\u0142aw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6263-9585","authenticated-orcid":false,"given":"Magdalena","family":"Skonieczna","sequence":"additional","affiliation":[{"name":"Department of Systems Biology and Engineering, The Silesian University of Technology, ul. Akademicka 16, 44-100 Gliwice, Poland"},{"name":"Biotechnology Centre, Silesian University of Technology, ul. Krzywoustego 8, 44-100 Gliwice, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrzej","family":"Po\u0142a","sequence":"additional","affiliation":[{"name":"Department of Biophysics and Neuroscience, Wroclaw Medical University, ul. Chalubinskiego 3a, 50-368 Wroclaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1659-3288","authenticated-orcid":false,"given":"Olga","family":"Weso\u0142owska","sequence":"additional","affiliation":[{"name":"Department of Biophysics and Neuroscience, Wroclaw Medical University, ul. Chalubinskiego 3a, 50-368 Wroclaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3454-5044","authenticated-orcid":false,"given":"Kamila","family":"\u015aroda-Pomianek","sequence":"additional","affiliation":[{"name":"Department of Biophysics and Neuroscience, Wroclaw Medical University, ul. Chalubinskiego 3a, 50-368 Wroclaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Kiokias, S., Proestos, C., and Oreopoulou, V. (2020). Phenolic Acids of Plant Origin-A Review on Their Antioxidant Activity In Vitro (O\/W Emulsion Systems) Along with Their in Vivo Health Biochemical Properties. Foods, 9.","DOI":"10.3390\/foods9040534"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"202","DOI":"10.3892\/ijmm.2014.1982","article-title":"Veratric acid inhibits iNOS expression through the regulation of PI3K activation and histone acetylation in LPS-stimulated RAW264.7 cells","volume":"35","author":"Choi","year":"2015","journal-title":"Int. J. Mol. 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