{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T17:36:02Z","timestamp":1770140162583,"version":"3.49.0"},"reference-count":176,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,4,8]],"date-time":"2025-04-08T00:00:00Z","timestamp":1744070400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Nucleu\u201d Program, UEFISCDI","award":["1N\/2023"],"award-info":[{"award-number":["1N\/2023"]}]},{"name":"Nucleu\u201d Program, UEFISCDI","award":["PN 23-28 04 01"],"award-info":[{"award-number":["PN 23-28 04 01"]}]},{"name":"MCID","award":["1N\/2023"],"award-info":[{"award-number":["1N\/2023"]}]},{"name":"MCID","award":["PN 23-28 04 01"],"award-info":[{"award-number":["PN 23-28 04 01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Plant extracts contain many small molecules that are less investigated. The present paper aims to study in silico physical-chemical, pharmacokinetic, medicinal chemistry and lead\/drug-likeness properties and the ability to interfere with the activity of P-glycoprotein (P-gp) transporter and cytochrome P450 (CYP) oxidase system in humans of phloridzin, phloretin, 4-methylchalcone metabolic series alongside the top three compounds found in the ethanolic extract from strawberries (S), namely 2,3-dihydro-3,5-dihydroxy-6-methyl-4H-pyran-4-one, 2-pyrrolidinone 5-(cyclohexylmethyl) and hexadecanoic acid. The phloridzin derivatives also were studied for their inhibitory potential upon Bcl-2, TNKS1 and COX-2 molecular targets. In vitro, Caco-2 studies analyzed the cytoprotective and anti-proliferative activity of S and the three phloridzin derivatives (pure compounds) in comparison with their combination 1:1 (GAE\/pure compound, w\/w), in the range 1 to 50 \u00b5g active compounds per test sample. Altogether, it was concluded that phloretin (Phl) can be used alone or in combination with S to support intestinal cell health in humans. Phloridzin (Phd) and phloridzin combined with S were proven ineffective. 4-methylchalcone (4-MeCh) combined with S indicated no advantages, while the pure compound exhibited augmented inhibitory effects, becoming a candidate for combinations with anticancer drugs. Overall, in silico studies revealed possible limitations in the practical use of phloridzin derivatives due to their potential to interfere with the activity of several major CYP enzymes.<\/jats:p>","DOI":"10.3390\/ijms26083492","type":"journal-article","created":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T05:03:07Z","timestamp":1744174987000},"page":"3492","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["In Silico and In Vitro Analyses of Strawberry-Derived Extracts in Relation to Key Compounds\u2019 Metabolic and Anti-Tumor Effects"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5032-5079","authenticated-orcid":false,"given":"Lucia Camelia","family":"Pirvu","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Biotechnologies, National Institute for Chemical Pharmaceutical Research and Development (INCDCF-ICCF), 112 Vitan, 031299 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7254-7991","authenticated-orcid":false,"given":"Amalia","family":"Stefaniu","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biotechnologies, National Institute for Chemical Pharmaceutical Research and Development (INCDCF-ICCF), 112 Vitan, 031299 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sultana","family":"Nita","sequence":"additional","affiliation":[{"name":"Department of Physical-Chemical Analysis and Quality Control, National Institute for Chemical Pharmaceutical Research and Development (INCDCF-ICCF), 112 Vitan, 031299 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1106-0258","authenticated-orcid":false,"given":"Nicoleta","family":"Radu","sequence":"additional","affiliation":[{"name":"Biotechnology Faculty, University of Agronomic Sciences and Veterinary Medicine of Bucharest, 59 Marasti, District 1, 011464 Bucharest, Romania"},{"name":"Department of Biotechnology, National Institute of Chemistry and Petrochemistry Research and Development, 202 Splaiul Independentei, 060021 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3087-3892","authenticated-orcid":false,"given":"Georgeta","family":"Neagu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, National Institute for Chemical Pharmaceutical Research and Development (INCDCF-ICCF), 112 Vitan, 031299 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"10582","DOI":"10.1039\/D4FO03618B","article-title":"Biological effects and mechanisms of dietary chalcones: Latest research progress, future research strategies, and challenges","volume":"21","author":"Zhang","year":"2024","journal-title":"Food Funct."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Kretzer, C., Jordan, P.M., Meyer, K.P.L., Hoff, D., Werner, M., Hofstetter, R.K., Koeberle, A., Cala Peralta, A., Viault, G., and Seraphin, D. 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