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N-phenyl-6-chloro-4-hydroxy-2-quinolone-3-carboxamides: Molecular Docking, Synthesis, and Biological Investigation as Anticancer Agents
Cancer is a multifactorial disease and the second leading cause of death worldwide. Diverse factors induce carcinogenesis, such as diet, smoking, radiation, and genetic defects. The phosphatidylinositol 3-kinase (PI3Kα) has emerged as an attractive target for anticancer drug design. Eighteen derivat...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7795513/ https://www.ncbi.nlm.nih.gov/pubmed/33375766 http://dx.doi.org/10.3390/molecules26010073 |
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author | Sabbah, Dima A. Haroon, Rawan A. Bardaweel, Sanaa K. Hajjo, Rima Sweidan, Kamal |
author_facet | Sabbah, Dima A. Haroon, Rawan A. Bardaweel, Sanaa K. Hajjo, Rima Sweidan, Kamal |
author_sort | Sabbah, Dima A. |
collection | PubMed |
description | Cancer is a multifactorial disease and the second leading cause of death worldwide. Diverse factors induce carcinogenesis, such as diet, smoking, radiation, and genetic defects. The phosphatidylinositol 3-kinase (PI3Kα) has emerged as an attractive target for anticancer drug design. Eighteen derivatives of N-phenyl-6-chloro-4-hydroxy-2-quinolone-3-carboxamide were synthesized and characterized using FT-IR, NMR ((1)H and (13)C), and high-resolution mass spectra (HRMS). The series exhibited distinct antiproliferative activity (IC(50) µM) against human epithelial colorectal adenocarcinoma (Caco-2) and colon carcinoma (HCT-116) cell lines, respectively: compounds 16 (37.4, 8.9 µM), 18 (50.9, 3.3 µM), 19 (17.0, 5.3 µM), and 21 (18.9, 4.9 µM). The induced-fit docking (IFD) studies against PI3Kαs showed that the derivatives occupy the PI3Kα binding site and engage with key binding residues. |
format | Online Article Text |
id | pubmed-7795513 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-77955132021-01-10 N-phenyl-6-chloro-4-hydroxy-2-quinolone-3-carboxamides: Molecular Docking, Synthesis, and Biological Investigation as Anticancer Agents Sabbah, Dima A. Haroon, Rawan A. Bardaweel, Sanaa K. Hajjo, Rima Sweidan, Kamal Molecules Article Cancer is a multifactorial disease and the second leading cause of death worldwide. Diverse factors induce carcinogenesis, such as diet, smoking, radiation, and genetic defects. The phosphatidylinositol 3-kinase (PI3Kα) has emerged as an attractive target for anticancer drug design. Eighteen derivatives of N-phenyl-6-chloro-4-hydroxy-2-quinolone-3-carboxamide were synthesized and characterized using FT-IR, NMR ((1)H and (13)C), and high-resolution mass spectra (HRMS). The series exhibited distinct antiproliferative activity (IC(50) µM) against human epithelial colorectal adenocarcinoma (Caco-2) and colon carcinoma (HCT-116) cell lines, respectively: compounds 16 (37.4, 8.9 µM), 18 (50.9, 3.3 µM), 19 (17.0, 5.3 µM), and 21 (18.9, 4.9 µM). The induced-fit docking (IFD) studies against PI3Kαs showed that the derivatives occupy the PI3Kα binding site and engage with key binding residues. MDPI 2020-12-25 /pmc/articles/PMC7795513/ /pubmed/33375766 http://dx.doi.org/10.3390/molecules26010073 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Sabbah, Dima A. Haroon, Rawan A. Bardaweel, Sanaa K. Hajjo, Rima Sweidan, Kamal N-phenyl-6-chloro-4-hydroxy-2-quinolone-3-carboxamides: Molecular Docking, Synthesis, and Biological Investigation as Anticancer Agents |
title | N-phenyl-6-chloro-4-hydroxy-2-quinolone-3-carboxamides: Molecular Docking, Synthesis, and Biological Investigation as Anticancer Agents |
title_full | N-phenyl-6-chloro-4-hydroxy-2-quinolone-3-carboxamides: Molecular Docking, Synthesis, and Biological Investigation as Anticancer Agents |
title_fullStr | N-phenyl-6-chloro-4-hydroxy-2-quinolone-3-carboxamides: Molecular Docking, Synthesis, and Biological Investigation as Anticancer Agents |
title_full_unstemmed | N-phenyl-6-chloro-4-hydroxy-2-quinolone-3-carboxamides: Molecular Docking, Synthesis, and Biological Investigation as Anticancer Agents |
title_short | N-phenyl-6-chloro-4-hydroxy-2-quinolone-3-carboxamides: Molecular Docking, Synthesis, and Biological Investigation as Anticancer Agents |
title_sort | n-phenyl-6-chloro-4-hydroxy-2-quinolone-3-carboxamides: molecular docking, synthesis, and biological investigation as anticancer agents |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7795513/ https://www.ncbi.nlm.nih.gov/pubmed/33375766 http://dx.doi.org/10.3390/molecules26010073 |
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