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The in silico studies were conducted using the Spartan\u201914 mechanistic program to perform a comparative analysis of the molecular, quantum and bioactivity parameters of the six analogues under study. The in vitro MTS studies were designed to investigate the cytotoxic and anti-proliferative effect of the reference substances (r.s.) of three main chalcone derivatives in nature, namely phloretin, phloridzin and 4-methylchalcone, on the Caco-2 cell line. Overall, the in silico results foremost suggested the potential of phloretin to traverse the blood\u2013brain barrier, and the abilities of phloridzin and nothofagin to act as broad cell enzyme inhibitors; the in vitro results demonstrated that phloretin and 4-methylchalcone have the potential to induce both cytotoxic and anti-proliferative effects, depending on their concentration level: the antiproliferative effects were noticed in the interval from 1 to 50 \u00b5g of r.s. per sample, while the cytotoxic effects were noticed from 1 to 50 \u00b5g of r.s. per sample in the case of 4-methychalcone, and at 50 \u00b5g of r.s. per sample in the case of phloretin. Phloridzin did not affect the viability of the Caco-2 line.<\/jats:p>","DOI":"10.3390\/sym16101383","type":"journal-article","created":{"date-parts":[[2024,10,17]],"date-time":"2024-10-17T08:56:32Z","timestamp":1729155392000},"page":"1383","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["In Silico Comparison of Quantum and Bioactivity Parameters of a Series of Natural Diphenyl Acetone Analogues, and In Vitro Caco-2 Studies on Three Main Chalcone Derivatives"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7254-7991","authenticated-orcid":false,"given":"Amalia","family":"Stefaniu","sequence":"first","affiliation":[{"name":"National Institute of Chemical Pharmaceutical Research and Development, ICCF-Bucharest, 112 Vitan, 031299 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":"National Institute of Chemical Pharmaceutical Research and Development, ICCF-Bucharest, 112 Vitan, 031299 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adrian","family":"Albulescu","sequence":"additional","affiliation":[{"name":"National Institute of Chemical Pharmaceutical Research and Development, ICCF-Bucharest, 112 Vitan, 031299 Bucharest, Romania"},{"name":"Stefan S. Nicolau Institute of Virology, 285 Mihai Bravu, 030304 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":"Biotechnology Department, National Institute of Chemistry and Petrochemistry Research and Development, 202 Splaiul Independentei, District 6, 031299 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5032-5079","authenticated-orcid":false,"given":"Lucia Camelia","family":"Pirvu","sequence":"additional","affiliation":[{"name":"National Institute of Chemical Pharmaceutical Research and Development, ICCF-Bucharest, 112 Vitan, 031299 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"9908","DOI":"10.1021\/la301653s","article-title":"Effect of dipole modifiers on the magnitude of the dipole potential of sterol-containing bilayers","volume":"28","author":"Efimova","year":"2012","journal-title":"Langmuir"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"7409","DOI":"10.1021\/acs.chemrev.7b00678","article-title":"Intracellular Delivery by Membrane Disruption: Mechanisms, Strategies, and Concepts","volume":"118","author":"Stewart","year":"2018","journal-title":"Chem. 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