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Recruitment of hexahydroquinoline as anticancer scaffold targeting inhibition of wild and mutants EGFR (EGFR(WT), EGFR(T790M), and EGFR(L858R))
Hexahydroquinoline (HHQ) scaffold was constructed and recruited for development of new series of anticancer agents. Thirty-two new compounds were synthesised where x-ray crystallography was performed to confirm enantiomerism. Thirteen compounds showed moderate to good activity against NCI 60 cancer...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Taylor & Francis
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10408569/ https://www.ncbi.nlm.nih.gov/pubmed/37548154 http://dx.doi.org/10.1080/14756366.2023.2241674 |
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author | Abo Al-Hamd, Mahmoud G. Tawfik, Haytham O. Abdullah, Omeima Yamaguchi, Koki Sugiura, Masaharu Mehany, Ahmed B. M. El-Hamamsy, Mervat H. El-Moselhy, Tarek F. |
author_facet | Abo Al-Hamd, Mahmoud G. Tawfik, Haytham O. Abdullah, Omeima Yamaguchi, Koki Sugiura, Masaharu Mehany, Ahmed B. M. El-Hamamsy, Mervat H. El-Moselhy, Tarek F. |
author_sort | Abo Al-Hamd, Mahmoud G. |
collection | PubMed |
description | Hexahydroquinoline (HHQ) scaffold was constructed and recruited for development of new series of anticancer agents. Thirty-two new compounds were synthesised where x-ray crystallography was performed to confirm enantiomerism. Thirteen compounds showed moderate to good activity against NCI 60 cancer cell lines, with GI % mean up to 74% for 10c. Expending erlotinib as a reference drug, target compounds were verified for their inhibiting activities against EGFR(WT), EGFR(T790M), and EGFR(L858R) where compound 10d was the best inhibitor with IC(50) = 0.097, 0.280, and 0.051 µM, respectively, compared to erlotinib (IC(50) = 0.082 µM, 0.342 µM, and 0.055 µM, respectively). Safety profile was validated using normal human lung (IMR-90) cells. 10c and 10d disrupted cell cycle at pre-G1 and G2/M phases in lung cancer, HOP-92, and cell line. Molecular docking study was achieved to understand the potential binding interactions and affinities in the active sites of three versions of EGFRs. |
format | Online Article Text |
id | pubmed-10408569 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-104085692023-08-09 Recruitment of hexahydroquinoline as anticancer scaffold targeting inhibition of wild and mutants EGFR (EGFR(WT), EGFR(T790M), and EGFR(L858R)) Abo Al-Hamd, Mahmoud G. Tawfik, Haytham O. Abdullah, Omeima Yamaguchi, Koki Sugiura, Masaharu Mehany, Ahmed B. M. El-Hamamsy, Mervat H. El-Moselhy, Tarek F. J Enzyme Inhib Med Chem Research Article Hexahydroquinoline (HHQ) scaffold was constructed and recruited for development of new series of anticancer agents. Thirty-two new compounds were synthesised where x-ray crystallography was performed to confirm enantiomerism. Thirteen compounds showed moderate to good activity against NCI 60 cancer cell lines, with GI % mean up to 74% for 10c. Expending erlotinib as a reference drug, target compounds were verified for their inhibiting activities against EGFR(WT), EGFR(T790M), and EGFR(L858R) where compound 10d was the best inhibitor with IC(50) = 0.097, 0.280, and 0.051 µM, respectively, compared to erlotinib (IC(50) = 0.082 µM, 0.342 µM, and 0.055 µM, respectively). Safety profile was validated using normal human lung (IMR-90) cells. 10c and 10d disrupted cell cycle at pre-G1 and G2/M phases in lung cancer, HOP-92, and cell line. Molecular docking study was achieved to understand the potential binding interactions and affinities in the active sites of three versions of EGFRs. Taylor & Francis 2023-08-07 /pmc/articles/PMC10408569/ /pubmed/37548154 http://dx.doi.org/10.1080/14756366.2023.2241674 Text en © 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The terms on which this article has been published allow the posting of the Accepted Manuscript in a repository by the author(s) or with their consent. |
spellingShingle | Research Article Abo Al-Hamd, Mahmoud G. Tawfik, Haytham O. Abdullah, Omeima Yamaguchi, Koki Sugiura, Masaharu Mehany, Ahmed B. M. El-Hamamsy, Mervat H. El-Moselhy, Tarek F. Recruitment of hexahydroquinoline as anticancer scaffold targeting inhibition of wild and mutants EGFR (EGFR(WT), EGFR(T790M), and EGFR(L858R)) |
title | Recruitment of hexahydroquinoline as anticancer scaffold targeting inhibition of wild and mutants EGFR (EGFR(WT), EGFR(T790M), and EGFR(L858R)) |
title_full | Recruitment of hexahydroquinoline as anticancer scaffold targeting inhibition of wild and mutants EGFR (EGFR(WT), EGFR(T790M), and EGFR(L858R)) |
title_fullStr | Recruitment of hexahydroquinoline as anticancer scaffold targeting inhibition of wild and mutants EGFR (EGFR(WT), EGFR(T790M), and EGFR(L858R)) |
title_full_unstemmed | Recruitment of hexahydroquinoline as anticancer scaffold targeting inhibition of wild and mutants EGFR (EGFR(WT), EGFR(T790M), and EGFR(L858R)) |
title_short | Recruitment of hexahydroquinoline as anticancer scaffold targeting inhibition of wild and mutants EGFR (EGFR(WT), EGFR(T790M), and EGFR(L858R)) |
title_sort | recruitment of hexahydroquinoline as anticancer scaffold targeting inhibition of wild and mutants egfr (egfr(wt), egfr(t790m), and egfr(l858r)) |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10408569/ https://www.ncbi.nlm.nih.gov/pubmed/37548154 http://dx.doi.org/10.1080/14756366.2023.2241674 |
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