Cargando…
Chalcones as Promising Antitumor Agents by Targeting the p53 Pathway: An Overview and New Insights in Drug-Likeness
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)...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8233907/ https://www.ncbi.nlm.nih.gov/pubmed/34205272 http://dx.doi.org/10.3390/molecules26123737 |
_version_ | 1783713959198588928 |
---|---|
author | Moreira, Joana Almeida, Joana Saraiva, Lucília Cidade, Honorina Pinto, Madalena |
author_facet | Moreira, Joana Almeida, Joana Saraiva, Lucília Cidade, Honorina Pinto, Madalena |
author_sort | Moreira, Joana |
collection | PubMed |
description | 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–MDM2 interaction inhibitors were accomplished considering molecular descriptors, biophysiochemical properties, and pharmacokinetic parameters in comparison with those from p53–MDM2 in clinical trials. With this review, we expect to guide the design of new and more effective chalcones targeting the p53 pathway. |
format | Online Article Text |
id | pubmed-8233907 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-82339072021-06-27 Chalcones as Promising Antitumor Agents by Targeting the p53 Pathway: An Overview and New Insights in Drug-Likeness Moreira, Joana Almeida, Joana Saraiva, Lucília Cidade, Honorina Pinto, Madalena Molecules Review 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–MDM2 interaction inhibitors were accomplished considering molecular descriptors, biophysiochemical properties, and pharmacokinetic parameters in comparison with those from p53–MDM2 in clinical trials. With this review, we expect to guide the design of new and more effective chalcones targeting the p53 pathway. MDPI 2021-06-19 /pmc/articles/PMC8233907/ /pubmed/34205272 http://dx.doi.org/10.3390/molecules26123737 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Moreira, Joana Almeida, Joana Saraiva, Lucília Cidade, Honorina Pinto, Madalena Chalcones as Promising Antitumor Agents by Targeting the p53 Pathway: An Overview and New Insights in Drug-Likeness |
title | Chalcones as Promising Antitumor Agents by Targeting the p53 Pathway: An Overview and New Insights in Drug-Likeness |
title_full | Chalcones as Promising Antitumor Agents by Targeting the p53 Pathway: An Overview and New Insights in Drug-Likeness |
title_fullStr | Chalcones as Promising Antitumor Agents by Targeting the p53 Pathway: An Overview and New Insights in Drug-Likeness |
title_full_unstemmed | Chalcones as Promising Antitumor Agents by Targeting the p53 Pathway: An Overview and New Insights in Drug-Likeness |
title_short | Chalcones as Promising Antitumor Agents by Targeting the p53 Pathway: An Overview and New Insights in Drug-Likeness |
title_sort | chalcones as promising antitumor agents by targeting the p53 pathway: an overview and new insights in drug-likeness |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8233907/ https://www.ncbi.nlm.nih.gov/pubmed/34205272 http://dx.doi.org/10.3390/molecules26123737 |
work_keys_str_mv | AT moreirajoana chalconesaspromisingantitumoragentsbytargetingthep53pathwayanoverviewandnewinsightsindruglikeness AT almeidajoana chalconesaspromisingantitumoragentsbytargetingthep53pathwayanoverviewandnewinsightsindruglikeness AT saraivalucilia chalconesaspromisingantitumoragentsbytargetingthep53pathwayanoverviewandnewinsightsindruglikeness AT cidadehonorina chalconesaspromisingantitumoragentsbytargetingthep53pathwayanoverviewandnewinsightsindruglikeness AT pintomadalena chalconesaspromisingantitumoragentsbytargetingthep53pathwayanoverviewandnewinsightsindruglikeness |