{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T20:47:08Z","timestamp":1778273228494,"version":"3.51.4"},"reference-count":88,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,6,19]],"date-time":"2021-06-19T00:00:00Z","timestamp":1624060800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["UIDB\/04423\/2020, UIDP\/04423\/2020, UIDB\/50006\/2020, PTDC\/SAU-PUB\/28736\/2017"],"award-info":[{"award-number":["UIDB\/04423\/2020, UIDP\/04423\/2020, UIDB\/50006\/2020, PTDC\/SAU-PUB\/28736\/2017"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The p53 protein is one of the most important tumor suppressors that are frequently inactivated in cancer cells. This inactivation occurs either because the TP53 gene is mutated or deleted, or due to the p53 protein inhibition by endogenous negative regulators, particularly murine double minute (MDM)2. Therefore, the reestablishment of p53 activity has received great attention concerning the discovery of new cancer therapeutics. Chalcones are naturally occurring compounds widely described as potential antitumor agents through several mechanisms, including those involving the p53 pathway. The inhibitory effect of these compounds in the interaction between p53 and MDM2 has also been recognized, with this effect associated with binding to a subsite of the p53 binding cleft of MDM2. In this work, a literature review of natural and synthetic chalcones and their analogues potentially interfering with p53 pathway is presented. Moreover, in silico studies of drug-likeness of chalcones recognized as p53\u2013MDM2 interaction inhibitors were accomplished considering molecular descriptors, biophysiochemical properties, and pharmacokinetic parameters in comparison with those from p53\u2013MDM2 in clinical trials. With this review, we expect to guide the design of new and more effective chalcones targeting the p53 pathway.<\/jats:p>","DOI":"10.3390\/molecules26123737","type":"journal-article","created":{"date-parts":[[2021,6,20]],"date-time":"2021-06-20T21:50:15Z","timestamp":1624225815000},"page":"3737","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Chalcones as Promising Antitumor Agents by Targeting the p53 Pathway: An Overview and New Insights in Drug-Likeness"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9883-8412","authenticated-orcid":false,"given":"Joana","family":"Moreira","sequence":"first","affiliation":[{"name":"Laboratory of Organic and Pharmaceutical Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"},{"name":"Interdisciplinary Centre of Marine and Environmental Research (CIIMAR), University of Porto, Edif\u00edcio do Terminal de Cruzeiros do Porto de Leix\u00f5es, Avenida General Norton de Matos s\/n, 4450-208 Matosinhos, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2325-5439","authenticated-orcid":false,"given":"Joana","family":"Almeida","sequence":"additional","affiliation":[{"name":"LAQV\/REQUIMTE, Laboratory of Microbiology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9531-4939","authenticated-orcid":false,"given":"Luc\u00edlia","family":"Saraiva","sequence":"additional","affiliation":[{"name":"LAQV\/REQUIMTE, Laboratory of Microbiology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0715-1779","authenticated-orcid":false,"given":"Honorina","family":"Cidade","sequence":"additional","affiliation":[{"name":"Laboratory of Organic and Pharmaceutical Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"},{"name":"Interdisciplinary Centre of Marine and Environmental Research (CIIMAR), University of Porto, Edif\u00edcio do Terminal de Cruzeiros do Porto de Leix\u00f5es, Avenida General Norton de Matos s\/n, 4450-208 Matosinhos, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4676-1409","authenticated-orcid":false,"given":"Madalena","family":"Pinto","sequence":"additional","affiliation":[{"name":"Laboratory of Organic and Pharmaceutical Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"},{"name":"Interdisciplinary Centre of Marine and Environmental Research (CIIMAR), University of Porto, Edif\u00edcio do Terminal de Cruzeiros do Porto de Leix\u00f5es, Avenida General Norton de Matos s\/n, 4450-208 Matosinhos, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7762","DOI":"10.1021\/acs.chemrev.7b00020","article-title":"Chalcone: A privileged structure in medicinal chemistry","volume":"117","author":"Zhuang","year":"2017","journal-title":"Chem. 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