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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...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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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. |
format | Online Article Text |
id | pubmed-8469912 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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