Cargando…
Benzo[g]quinazolin-based scaffold derivatives as dual EGFR/HER2 inhibitors
Targeting EGFR has proven to be beneficial in the treatment of several types of solid tumours. So, a series of novel 2-(4-oxo-3-(4-sulfamoylphenyl)-3,4-dihydrobenzo[g]quinazolin-2-ylthio)-N-substituted acetamide 5–19 were synthesised from the starting material 4-(2-mercapto-4-oxobenzo[g]quinazolin-3...
Autores principales: | , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2017
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6010119/ https://www.ncbi.nlm.nih.gov/pubmed/29098904 http://dx.doi.org/10.1080/14756366.2017.1389922 |
_version_ | 1783333528596905984 |
---|---|
author | Ghorab, Mostafa M. Alsaid, Mansour S. Soliman, Aiten M. Al-Mishari, Abdullah A. |
author_facet | Ghorab, Mostafa M. Alsaid, Mansour S. Soliman, Aiten M. Al-Mishari, Abdullah A. |
author_sort | Ghorab, Mostafa M. |
collection | PubMed |
description | Targeting EGFR has proven to be beneficial in the treatment of several types of solid tumours. So, a series of novel 2-(4-oxo-3-(4-sulfamoylphenyl)-3,4-dihydrobenzo[g]quinazolin-2-ylthio)-N-substituted acetamide 5–19 were synthesised from the starting material 4-(2-mercapto-4-oxobenzo[g]quinazolin-3(4H)-yl) benzenesulfonamide 4, to be evaluated as dual EGFR/HER2 inhibitors. The target compounds 5–19, were screened for their cytotoxic activity against A549 lung cancer cell line. The percentage inhibition of EGFR enzyme was measured and compared with erlotinib as the reference drug. Compounds 6, 8, 10, and 16 showed excellent EGFR inhibitory activity and were further selected for screening as dual EGFR/HER2 inhibitors. The four selected compounds showed IC(50) ranging from 0.009 to 0.026 µM for EGFR and 0.021 to 0.069 µM for the HER2 enzyme. Compound 8 was found to be the most potent in this study with IC(50) 0.009 and 0.021 µM for EGFR and HER2, respectively. |
format | Online Article Text |
id | pubmed-6010119 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-60101192018-07-11 Benzo[g]quinazolin-based scaffold derivatives as dual EGFR/HER2 inhibitors Ghorab, Mostafa M. Alsaid, Mansour S. Soliman, Aiten M. Al-Mishari, Abdullah A. J Enzyme Inhib Med Chem Research Paper Targeting EGFR has proven to be beneficial in the treatment of several types of solid tumours. So, a series of novel 2-(4-oxo-3-(4-sulfamoylphenyl)-3,4-dihydrobenzo[g]quinazolin-2-ylthio)-N-substituted acetamide 5–19 were synthesised from the starting material 4-(2-mercapto-4-oxobenzo[g]quinazolin-3(4H)-yl) benzenesulfonamide 4, to be evaluated as dual EGFR/HER2 inhibitors. The target compounds 5–19, were screened for their cytotoxic activity against A549 lung cancer cell line. The percentage inhibition of EGFR enzyme was measured and compared with erlotinib as the reference drug. Compounds 6, 8, 10, and 16 showed excellent EGFR inhibitory activity and were further selected for screening as dual EGFR/HER2 inhibitors. The four selected compounds showed IC(50) ranging from 0.009 to 0.026 µM for EGFR and 0.021 to 0.069 µM for the HER2 enzyme. Compound 8 was found to be the most potent in this study with IC(50) 0.009 and 0.021 µM for EGFR and HER2, respectively. Taylor & Francis 2017-11-03 /pmc/articles/PMC6010119/ /pubmed/29098904 http://dx.doi.org/10.1080/14756366.2017.1389922 Text en © 2017 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Paper Ghorab, Mostafa M. Alsaid, Mansour S. Soliman, Aiten M. Al-Mishari, Abdullah A. Benzo[g]quinazolin-based scaffold derivatives as dual EGFR/HER2 inhibitors |
title | Benzo[g]quinazolin-based scaffold derivatives as dual EGFR/HER2 inhibitors |
title_full | Benzo[g]quinazolin-based scaffold derivatives as dual EGFR/HER2 inhibitors |
title_fullStr | Benzo[g]quinazolin-based scaffold derivatives as dual EGFR/HER2 inhibitors |
title_full_unstemmed | Benzo[g]quinazolin-based scaffold derivatives as dual EGFR/HER2 inhibitors |
title_short | Benzo[g]quinazolin-based scaffold derivatives as dual EGFR/HER2 inhibitors |
title_sort | benzo[g]quinazolin-based scaffold derivatives as dual egfr/her2 inhibitors |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6010119/ https://www.ncbi.nlm.nih.gov/pubmed/29098904 http://dx.doi.org/10.1080/14756366.2017.1389922 |
work_keys_str_mv | AT ghorabmostafam benzogquinazolinbasedscaffoldderivativesasdualegfrher2inhibitors AT alsaidmansours benzogquinazolinbasedscaffoldderivativesasdualegfrher2inhibitors AT solimanaitenm benzogquinazolinbasedscaffoldderivativesasdualegfrher2inhibitors AT almishariabdullaha benzogquinazolinbasedscaffoldderivativesasdualegfrher2inhibitors |