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Naproxen Based 1,3,4-Oxadiazole Derivatives as EGFR Inhibitors: Design, Synthesis, Anticancer, and Computational Studies

A library of novel naproxen based 1,3,4-oxadiazole derivatives (8–16 and 19–26) has been synthesized and screened for cytotoxicity as EGFR inhibitors. Among the synthesized hybrids, compound2-(4-((5-((S)-1-(2-methoxynaphthalen-6-yl)ethyl)-1,3,4-oxadiazol-2-ylthio)methyl)-1H-1,2,3-triazol-1-yl)phenol...

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Autores principales: Alam, Mohammad Mahboob, Nazreen, Syed, Almalki, Abdulraheem S. A., Elhenawy, Ahmed A., Alsenani, Nawaf I., Elbehairi, Serag Eldin I., Malebari, Azizah M., Alfaifi, Mohammad Y., Alsharif, Meshari A., Alfaifi, Sulaiman Y. M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8469912/
https://www.ncbi.nlm.nih.gov/pubmed/34577570
http://dx.doi.org/10.3390/ph14090870
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author Alam, Mohammad Mahboob
Nazreen, Syed
Almalki, Abdulraheem S. A.
Elhenawy, Ahmed A.
Alsenani, Nawaf I.
Elbehairi, Serag Eldin I.
Malebari, Azizah M.
Alfaifi, Mohammad Y.
Alsharif, Meshari A.
Alfaifi, Sulaiman Y. M.
author_facet Alam, Mohammad Mahboob
Nazreen, Syed
Almalki, Abdulraheem S. A.
Elhenawy, Ahmed A.
Alsenani, Nawaf I.
Elbehairi, Serag Eldin I.
Malebari, Azizah M.
Alfaifi, Mohammad Y.
Alsharif, Meshari A.
Alfaifi, Sulaiman Y. M.
author_sort Alam, Mohammad Mahboob
collection PubMed
description A library of novel naproxen based 1,3,4-oxadiazole derivatives (8–16 and 19–26) has been synthesized and screened for cytotoxicity as EGFR inhibitors. Among the synthesized hybrids, compound2-(4-((5-((S)-1-(2-methoxynaphthalen-6-yl)ethyl)-1,3,4-oxadiazol-2-ylthio)methyl)-1H-1,2,3-triazol-1-yl)phenol(15) was the most potent compound against MCF-7 and HepG2cancer cells with IC(50) of 2.13 and 1.63 µg/mL, respectively, and was equipotent to doxorubicin (IC(50) 1.62 µg/mL) towards HepG2. Furthermore, compound 15 inhibited EGFR kinase with IC(50) 0.41 μM compared to standard drug Erlotinib (IC(50) 0.30 μM). The active compound induces a high percentage of necrosis towards MCF-7, HePG2 and HCT 116 cells. The docking studies, DFT and MEP also supported the biological data. These results demonstrated that these synthesized naproxen hybrids have EGFR inhibition effects and can be used as leads for cancer therapy.
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spelling pubmed-84699122021-09-27 Naproxen Based 1,3,4-Oxadiazole Derivatives as EGFR Inhibitors: Design, Synthesis, Anticancer, and Computational Studies Alam, Mohammad Mahboob Nazreen, Syed Almalki, Abdulraheem S. A. Elhenawy, Ahmed A. Alsenani, Nawaf I. Elbehairi, Serag Eldin I. Malebari, Azizah M. Alfaifi, Mohammad Y. Alsharif, Meshari A. Alfaifi, Sulaiman Y. M. Pharmaceuticals (Basel) Article A library of novel naproxen based 1,3,4-oxadiazole derivatives (8–16 and 19–26) has been synthesized and screened for cytotoxicity as EGFR inhibitors. Among the synthesized hybrids, compound2-(4-((5-((S)-1-(2-methoxynaphthalen-6-yl)ethyl)-1,3,4-oxadiazol-2-ylthio)methyl)-1H-1,2,3-triazol-1-yl)phenol(15) was the most potent compound against MCF-7 and HepG2cancer cells with IC(50) of 2.13 and 1.63 µg/mL, respectively, and was equipotent to doxorubicin (IC(50) 1.62 µg/mL) towards HepG2. Furthermore, compound 15 inhibited EGFR kinase with IC(50) 0.41 μM compared to standard drug Erlotinib (IC(50) 0.30 μM). The active compound induces a high percentage of necrosis towards MCF-7, HePG2 and HCT 116 cells. The docking studies, DFT and MEP also supported the biological data. These results demonstrated that these synthesized naproxen hybrids have EGFR inhibition effects and can be used as leads for cancer therapy. MDPI 2021-08-28 /pmc/articles/PMC8469912/ /pubmed/34577570 http://dx.doi.org/10.3390/ph14090870 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
Alam, Mohammad Mahboob
Nazreen, Syed
Almalki, Abdulraheem S. A.
Elhenawy, Ahmed A.
Alsenani, Nawaf I.
Elbehairi, Serag Eldin I.
Malebari, Azizah M.
Alfaifi, Mohammad Y.
Alsharif, Meshari A.
Alfaifi, Sulaiman Y. M.
Naproxen Based 1,3,4-Oxadiazole Derivatives as EGFR Inhibitors: Design, Synthesis, Anticancer, and Computational Studies
title Naproxen Based 1,3,4-Oxadiazole Derivatives as EGFR Inhibitors: Design, Synthesis, Anticancer, and Computational Studies
title_full Naproxen Based 1,3,4-Oxadiazole Derivatives as EGFR Inhibitors: Design, Synthesis, Anticancer, and Computational Studies
title_fullStr Naproxen Based 1,3,4-Oxadiazole Derivatives as EGFR Inhibitors: Design, Synthesis, Anticancer, and Computational Studies
title_full_unstemmed Naproxen Based 1,3,4-Oxadiazole Derivatives as EGFR Inhibitors: Design, Synthesis, Anticancer, and Computational Studies
title_short Naproxen Based 1,3,4-Oxadiazole Derivatives as EGFR Inhibitors: Design, Synthesis, Anticancer, and Computational Studies
title_sort naproxen based 1,3,4-oxadiazole derivatives as egfr inhibitors: design, synthesis, anticancer, and computational studies
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8469912/
https://www.ncbi.nlm.nih.gov/pubmed/34577570
http://dx.doi.org/10.3390/ph14090870
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