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Synthesis, Anticancer Screening of Some Novel Trimethoxy Quinazolines and VEGFR2, EGFR Tyrosine Kinase Inhibitors Assay; Molecular Docking Studies

A new series of 8-methoxy-2-trimethoxyphenyl-3-substituted quinazoline-4(3)-one compounds were designed, synthesized, and screened for antitumor activity against three cell lines, namely, Hela, A549, and MDA compared to docetaxel as reference drug. The molecular docking was performed using Autodock...

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Autores principales: Altamimi, Abdulmalik S., El-Azab, Adel S., Abdelhamid, Sami G., Alamri, Mubarak A., Bayoumi, Ashraf H., Alqahtani, Safar M., Alabbas, Alhumaidi B., Altharawi, Ali I., Alossaimi, Manal A., Mohamed, Menshawy A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8157871/
https://www.ncbi.nlm.nih.gov/pubmed/34069962
http://dx.doi.org/10.3390/molecules26102992
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author Altamimi, Abdulmalik S.
El-Azab, Adel S.
Abdelhamid, Sami G.
Alamri, Mubarak A.
Bayoumi, Ashraf H.
Alqahtani, Safar M.
Alabbas, Alhumaidi B.
Altharawi, Ali I.
Alossaimi, Manal A.
Mohamed, Menshawy A.
author_facet Altamimi, Abdulmalik S.
El-Azab, Adel S.
Abdelhamid, Sami G.
Alamri, Mubarak A.
Bayoumi, Ashraf H.
Alqahtani, Safar M.
Alabbas, Alhumaidi B.
Altharawi, Ali I.
Alossaimi, Manal A.
Mohamed, Menshawy A.
author_sort Altamimi, Abdulmalik S.
collection PubMed
description A new series of 8-methoxy-2-trimethoxyphenyl-3-substituted quinazoline-4(3)-one compounds were designed, synthesized, and screened for antitumor activity against three cell lines, namely, Hela, A549, and MDA compared to docetaxel as reference drug. The molecular docking was performed using Autodock Vina program and 20 ns molecular dynamics (MD) simulation was performed using GROMACS 2018.1 software. Compound 6 was the most potent antitumor of the new synthesized compounds and was evaluated as a VEGFR2 and EGFR inhibitor with (IC50, 98.1 and 106 nM respectively) compared to docetaxel (IC50, 89.3 and 56.1 nM respectively). Compounds 2, 6, 10, and 8 showed strong cytotoxic activities against the Hela cell line with IC50 of, 2.13, 2.8, 3.98, and 4.94 µM, respectively, relative to docetaxel (IC50, 9.65 µM). Compound 11 showed strong cytotoxic activity against A549 cell line (IC50, 4.03 µM) relative to docetaxel (IC50, 10.8 µM). Whereas compounds 6 and 9 showed strong cytotoxic activity against MDA cell line (IC50, 0.79, 3.42 µM, respectively) as compared to docetaxel (IC50, 3.98 µM).
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spelling pubmed-81578712021-05-28 Synthesis, Anticancer Screening of Some Novel Trimethoxy Quinazolines and VEGFR2, EGFR Tyrosine Kinase Inhibitors Assay; Molecular Docking Studies Altamimi, Abdulmalik S. El-Azab, Adel S. Abdelhamid, Sami G. Alamri, Mubarak A. Bayoumi, Ashraf H. Alqahtani, Safar M. Alabbas, Alhumaidi B. Altharawi, Ali I. Alossaimi, Manal A. Mohamed, Menshawy A. Molecules Article A new series of 8-methoxy-2-trimethoxyphenyl-3-substituted quinazoline-4(3)-one compounds were designed, synthesized, and screened for antitumor activity against three cell lines, namely, Hela, A549, and MDA compared to docetaxel as reference drug. The molecular docking was performed using Autodock Vina program and 20 ns molecular dynamics (MD) simulation was performed using GROMACS 2018.1 software. Compound 6 was the most potent antitumor of the new synthesized compounds and was evaluated as a VEGFR2 and EGFR inhibitor with (IC50, 98.1 and 106 nM respectively) compared to docetaxel (IC50, 89.3 and 56.1 nM respectively). Compounds 2, 6, 10, and 8 showed strong cytotoxic activities against the Hela cell line with IC50 of, 2.13, 2.8, 3.98, and 4.94 µM, respectively, relative to docetaxel (IC50, 9.65 µM). Compound 11 showed strong cytotoxic activity against A549 cell line (IC50, 4.03 µM) relative to docetaxel (IC50, 10.8 µM). Whereas compounds 6 and 9 showed strong cytotoxic activity against MDA cell line (IC50, 0.79, 3.42 µM, respectively) as compared to docetaxel (IC50, 3.98 µM). MDPI 2021-05-18 /pmc/articles/PMC8157871/ /pubmed/34069962 http://dx.doi.org/10.3390/molecules26102992 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 Article
Altamimi, Abdulmalik S.
El-Azab, Adel S.
Abdelhamid, Sami G.
Alamri, Mubarak A.
Bayoumi, Ashraf H.
Alqahtani, Safar M.
Alabbas, Alhumaidi B.
Altharawi, Ali I.
Alossaimi, Manal A.
Mohamed, Menshawy A.
Synthesis, Anticancer Screening of Some Novel Trimethoxy Quinazolines and VEGFR2, EGFR Tyrosine Kinase Inhibitors Assay; Molecular Docking Studies
title Synthesis, Anticancer Screening of Some Novel Trimethoxy Quinazolines and VEGFR2, EGFR Tyrosine Kinase Inhibitors Assay; Molecular Docking Studies
title_full Synthesis, Anticancer Screening of Some Novel Trimethoxy Quinazolines and VEGFR2, EGFR Tyrosine Kinase Inhibitors Assay; Molecular Docking Studies
title_fullStr Synthesis, Anticancer Screening of Some Novel Trimethoxy Quinazolines and VEGFR2, EGFR Tyrosine Kinase Inhibitors Assay; Molecular Docking Studies
title_full_unstemmed Synthesis, Anticancer Screening of Some Novel Trimethoxy Quinazolines and VEGFR2, EGFR Tyrosine Kinase Inhibitors Assay; Molecular Docking Studies
title_short Synthesis, Anticancer Screening of Some Novel Trimethoxy Quinazolines and VEGFR2, EGFR Tyrosine Kinase Inhibitors Assay; Molecular Docking Studies
title_sort synthesis, anticancer screening of some novel trimethoxy quinazolines and vegfr2, egfr tyrosine kinase inhibitors assay; molecular docking studies
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8157871/
https://www.ncbi.nlm.nih.gov/pubmed/34069962
http://dx.doi.org/10.3390/molecules26102992
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