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Impact of trifluoromethyl and sulfonyl groups on the biological activity of novel aryl-urea derivatives: synthesis, in-vitro, in-silico and SAR studies
We designed and prepared a novel series of urea derivatives with/without sulfonyl group in their structures to investigate the impact of the sulfonyl group on the biological activity of the evaluated compounds. Antibacterial investigations indicated that derivatives 7, 8, 9, and 11 had the most anti...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10579241/ https://www.ncbi.nlm.nih.gov/pubmed/37845243 http://dx.doi.org/10.1038/s41598-023-44753-9 |
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author | Sroor, Farid M. Mahrous, Karima F. El-Kader, Heba A. M. Abd Othman, Abdelmageed M. Ibrahim, Nada S. |
author_facet | Sroor, Farid M. Mahrous, Karima F. El-Kader, Heba A. M. Abd Othman, Abdelmageed M. Ibrahim, Nada S. |
author_sort | Sroor, Farid M. |
collection | PubMed |
description | We designed and prepared a novel series of urea derivatives with/without sulfonyl group in their structures to investigate the impact of the sulfonyl group on the biological activity of the evaluated compounds. Antibacterial investigations indicated that derivatives 7, 8, 9, and 11 had the most antibacterial property of all the compounds examined, their minimum inhibitory concentrations (MICs) determined against B. mycoides, E. coli, and C. albicans, with compound 8 being the most active at a MIC value of 4.88 µg/mL. Anti-cancer activity has been tested against eight human cancer cell lines; A549, HCT116, PC3, A431, HePG2, HOS, PACA2 and BJ1. Compounds 7, 8 and 9 emerged IC(50) values better than Doxorubicin as a reference drug. Compounds 7 and 8 showed IC(50) = 44.4 and 22.4 μM respectively against PACA2 compared to Doxorubicin (IC(50) = 52.1 μM). Compound 9 showed IC(50) = 17.8, 12.4, and 17.6 μM against HCT116, HePG2, and HOS, respectively. qRT-PCR revealed the down-regulation of PALB2 in compounds 7 and 15 treated PACA2 cells. Also, the down-regulation of BRCA1 and BRCA2 was shown in compound 7 treated PC3 cells. As regard A549 cells, compound 8 decreased the expression level of EGFR and KRAS genes. While compounds 7 and 9 down-regulated TP53 and FASN in HCT116 cells. Molecular docking was done against Escherichia coli enoyl reductase and human Son of sevenless homolog 1 (SOS1) and the results showed the promising inhibition of the studied proteins. |
format | Online Article Text |
id | pubmed-10579241 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-105792412023-10-18 Impact of trifluoromethyl and sulfonyl groups on the biological activity of novel aryl-urea derivatives: synthesis, in-vitro, in-silico and SAR studies Sroor, Farid M. Mahrous, Karima F. El-Kader, Heba A. M. Abd Othman, Abdelmageed M. Ibrahim, Nada S. Sci Rep Article We designed and prepared a novel series of urea derivatives with/without sulfonyl group in their structures to investigate the impact of the sulfonyl group on the biological activity of the evaluated compounds. Antibacterial investigations indicated that derivatives 7, 8, 9, and 11 had the most antibacterial property of all the compounds examined, their minimum inhibitory concentrations (MICs) determined against B. mycoides, E. coli, and C. albicans, with compound 8 being the most active at a MIC value of 4.88 µg/mL. Anti-cancer activity has been tested against eight human cancer cell lines; A549, HCT116, PC3, A431, HePG2, HOS, PACA2 and BJ1. Compounds 7, 8 and 9 emerged IC(50) values better than Doxorubicin as a reference drug. Compounds 7 and 8 showed IC(50) = 44.4 and 22.4 μM respectively against PACA2 compared to Doxorubicin (IC(50) = 52.1 μM). Compound 9 showed IC(50) = 17.8, 12.4, and 17.6 μM against HCT116, HePG2, and HOS, respectively. qRT-PCR revealed the down-regulation of PALB2 in compounds 7 and 15 treated PACA2 cells. Also, the down-regulation of BRCA1 and BRCA2 was shown in compound 7 treated PC3 cells. As regard A549 cells, compound 8 decreased the expression level of EGFR and KRAS genes. While compounds 7 and 9 down-regulated TP53 and FASN in HCT116 cells. Molecular docking was done against Escherichia coli enoyl reductase and human Son of sevenless homolog 1 (SOS1) and the results showed the promising inhibition of the studied proteins. Nature Publishing Group UK 2023-10-16 /pmc/articles/PMC10579241/ /pubmed/37845243 http://dx.doi.org/10.1038/s41598-023-44753-9 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Sroor, Farid M. Mahrous, Karima F. El-Kader, Heba A. M. Abd Othman, Abdelmageed M. Ibrahim, Nada S. Impact of trifluoromethyl and sulfonyl groups on the biological activity of novel aryl-urea derivatives: synthesis, in-vitro, in-silico and SAR studies |
title | Impact of trifluoromethyl and sulfonyl groups on the biological activity of novel aryl-urea derivatives: synthesis, in-vitro, in-silico and SAR studies |
title_full | Impact of trifluoromethyl and sulfonyl groups on the biological activity of novel aryl-urea derivatives: synthesis, in-vitro, in-silico and SAR studies |
title_fullStr | Impact of trifluoromethyl and sulfonyl groups on the biological activity of novel aryl-urea derivatives: synthesis, in-vitro, in-silico and SAR studies |
title_full_unstemmed | Impact of trifluoromethyl and sulfonyl groups on the biological activity of novel aryl-urea derivatives: synthesis, in-vitro, in-silico and SAR studies |
title_short | Impact of trifluoromethyl and sulfonyl groups on the biological activity of novel aryl-urea derivatives: synthesis, in-vitro, in-silico and SAR studies |
title_sort | impact of trifluoromethyl and sulfonyl groups on the biological activity of novel aryl-urea derivatives: synthesis, in-vitro, in-silico and sar studies |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10579241/ https://www.ncbi.nlm.nih.gov/pubmed/37845243 http://dx.doi.org/10.1038/s41598-023-44753-9 |
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