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EGFR and COX-2 Dual Inhibitor: The Design, Synthesis, and Biological Evaluation of Novel Chalcones
For most researchers, discovering new anticancer drugs to avoid the adverse effects of current ones, to improve therapeutic benefits and to reduce resistance is essential. Because the COX-2 enzyme plays an important role in various types of cancer leading to malignancy enhancement, inhibition of apo...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8876975/ https://www.ncbi.nlm.nih.gov/pubmed/35208952 http://dx.doi.org/10.3390/molecules27041158 |
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author | Musa, Arafa Mostafa, Ehab M. Bukhari, Syed Nasir Abbas Alotaibi, Nasser Hadal El-Ghorab, Ahmed H. Farouk, Amr Nayl, AbdElAziz A. Ghoneim, Mohammed M. Abdelgawad, Mohamed A. |
author_facet | Musa, Arafa Mostafa, Ehab M. Bukhari, Syed Nasir Abbas Alotaibi, Nasser Hadal El-Ghorab, Ahmed H. Farouk, Amr Nayl, AbdElAziz A. Ghoneim, Mohammed M. Abdelgawad, Mohamed A. |
author_sort | Musa, Arafa |
collection | PubMed |
description | For most researchers, discovering new anticancer drugs to avoid the adverse effects of current ones, to improve therapeutic benefits and to reduce resistance is essential. Because the COX-2 enzyme plays an important role in various types of cancer leading to malignancy enhancement, inhibition of apoptosis, and tumor-cell metastasis, an indispensable objective is to design new scaffolds or drugs that possess combined action or dual effect, such as kinase and COX-2 inhibition. The start compounds A1 to A6 were prepared through the diazo coupling of 3-aminoacetophenone with a corresponding phenol and then condensed with two new chalcone series, C7–18. The newly synthesized compounds were assessed against both COX-2 and epidermal growth factor receptor (EGFR) for their inhibitory effect. All novel compounds were screened for cytotoxicity against five cancer cell lines. Compounds C9 and G10 exhibited potent EGFR inhibition with IC(50) values of 0.8 and 1.1 µM, respectively. Additionally, they also displayed great COX-2 inhibition with IC(50) values of 1.27 and 1.88 µM, respectively. Furthermore, the target compounds were assessed for their cytotoxicity against pancreatic ductal cancer (Panc-1), lung cancer (H-460), human colon cancer (HT-29), human malignant melanoma (A375) and pancreatic cancer (PaCa-2) cell lines. Interestingly, compounds C10 and G12 exhibited the strongest cytotoxic effect against PaCa-2 with average IC(50) values of 0.9 and 0.8 µM, respectively. To understand the possible binding modes of the compounds under investigation with the receptor cites of EGFR and COX-2, a virtual docking study was conducted. |
format | Online Article Text |
id | pubmed-8876975 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-88769752022-02-26 EGFR and COX-2 Dual Inhibitor: The Design, Synthesis, and Biological Evaluation of Novel Chalcones Musa, Arafa Mostafa, Ehab M. Bukhari, Syed Nasir Abbas Alotaibi, Nasser Hadal El-Ghorab, Ahmed H. Farouk, Amr Nayl, AbdElAziz A. Ghoneim, Mohammed M. Abdelgawad, Mohamed A. Molecules Article For most researchers, discovering new anticancer drugs to avoid the adverse effects of current ones, to improve therapeutic benefits and to reduce resistance is essential. Because the COX-2 enzyme plays an important role in various types of cancer leading to malignancy enhancement, inhibition of apoptosis, and tumor-cell metastasis, an indispensable objective is to design new scaffolds or drugs that possess combined action or dual effect, such as kinase and COX-2 inhibition. The start compounds A1 to A6 were prepared through the diazo coupling of 3-aminoacetophenone with a corresponding phenol and then condensed with two new chalcone series, C7–18. The newly synthesized compounds were assessed against both COX-2 and epidermal growth factor receptor (EGFR) for their inhibitory effect. All novel compounds were screened for cytotoxicity against five cancer cell lines. Compounds C9 and G10 exhibited potent EGFR inhibition with IC(50) values of 0.8 and 1.1 µM, respectively. Additionally, they also displayed great COX-2 inhibition with IC(50) values of 1.27 and 1.88 µM, respectively. Furthermore, the target compounds were assessed for their cytotoxicity against pancreatic ductal cancer (Panc-1), lung cancer (H-460), human colon cancer (HT-29), human malignant melanoma (A375) and pancreatic cancer (PaCa-2) cell lines. Interestingly, compounds C10 and G12 exhibited the strongest cytotoxic effect against PaCa-2 with average IC(50) values of 0.9 and 0.8 µM, respectively. To understand the possible binding modes of the compounds under investigation with the receptor cites of EGFR and COX-2, a virtual docking study was conducted. MDPI 2022-02-09 /pmc/articles/PMC8876975/ /pubmed/35208952 http://dx.doi.org/10.3390/molecules27041158 Text en © 2022 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 | Article Musa, Arafa Mostafa, Ehab M. Bukhari, Syed Nasir Abbas Alotaibi, Nasser Hadal El-Ghorab, Ahmed H. Farouk, Amr Nayl, AbdElAziz A. Ghoneim, Mohammed M. Abdelgawad, Mohamed A. EGFR and COX-2 Dual Inhibitor: The Design, Synthesis, and Biological Evaluation of Novel Chalcones |
title | EGFR and COX-2 Dual Inhibitor: The Design, Synthesis, and Biological Evaluation of Novel Chalcones |
title_full | EGFR and COX-2 Dual Inhibitor: The Design, Synthesis, and Biological Evaluation of Novel Chalcones |
title_fullStr | EGFR and COX-2 Dual Inhibitor: The Design, Synthesis, and Biological Evaluation of Novel Chalcones |
title_full_unstemmed | EGFR and COX-2 Dual Inhibitor: The Design, Synthesis, and Biological Evaluation of Novel Chalcones |
title_short | EGFR and COX-2 Dual Inhibitor: The Design, Synthesis, and Biological Evaluation of Novel Chalcones |
title_sort | egfr and cox-2 dual inhibitor: the design, synthesis, and biological evaluation of novel chalcones |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8876975/ https://www.ncbi.nlm.nih.gov/pubmed/35208952 http://dx.doi.org/10.3390/molecules27041158 |
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