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Design, synthesis, in vitro anticancer evaluation, kinase inhibitory effects, and pharmacokinetic profile of new 1,3,4-triarylpyrazole derivatives possessing terminal sulfonamide moiety
The present work describes the design and synthesis of a novel series of 1,3-diaryl-4-sulfonamidoarylpyrazole derivatives 1a–q and 2a–q and their in vitro biological activities. The target compounds were evaluated for antiproliferative activity against NCI-60 cell line panel. Compounds 1c, 1g, 1k–m,...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6211260/ https://www.ncbi.nlm.nih.gov/pubmed/30362383 http://dx.doi.org/10.1080/14756366.2018.1530225 |
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author | Abdel-Maksoud, Mohammed S. El-Gamal, Mohammed I. Gamal El-Din, Mahmoud M. Oh, Chang Hyun |
author_facet | Abdel-Maksoud, Mohammed S. El-Gamal, Mohammed I. Gamal El-Din, Mahmoud M. Oh, Chang Hyun |
author_sort | Abdel-Maksoud, Mohammed S. |
collection | PubMed |
description | The present work describes the design and synthesis of a novel series of 1,3-diaryl-4-sulfonamidoarylpyrazole derivatives 1a–q and 2a–q and their in vitro biological activities. The target compounds were evaluated for antiproliferative activity against NCI-60 cell line panel. Compounds 1c, 1g, 1k–m, 1o, 2g, 2h, 2k–m, 2o, and 2q showed the highest mean inhibition percentages at 10 µM single-dose testing and were selected to be tested at 5-dose mode. The ICs(50) of the most potent compounds were determined over the 60 cell lines. Compound 2l exhibited the strongest activity against different cell lines with IC(50) 0.33 µM against A498 renal cancer cell line. Compound 2l was tested over a panel of 20 kinases to determine its molecular target(s), and its IC(50) values over the most sensitive kinases were defined. In vitro stability and in vivo pharmacokinetic profile of compound 2l was also investigated. |
format | Online Article Text |
id | pubmed-6211260 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-62112602018-11-05 Design, synthesis, in vitro anticancer evaluation, kinase inhibitory effects, and pharmacokinetic profile of new 1,3,4-triarylpyrazole derivatives possessing terminal sulfonamide moiety Abdel-Maksoud, Mohammed S. El-Gamal, Mohammed I. Gamal El-Din, Mahmoud M. Oh, Chang Hyun J Enzyme Inhib Med Chem Research Paper The present work describes the design and synthesis of a novel series of 1,3-diaryl-4-sulfonamidoarylpyrazole derivatives 1a–q and 2a–q and their in vitro biological activities. The target compounds were evaluated for antiproliferative activity against NCI-60 cell line panel. Compounds 1c, 1g, 1k–m, 1o, 2g, 2h, 2k–m, 2o, and 2q showed the highest mean inhibition percentages at 10 µM single-dose testing and were selected to be tested at 5-dose mode. The ICs(50) of the most potent compounds were determined over the 60 cell lines. Compound 2l exhibited the strongest activity against different cell lines with IC(50) 0.33 µM against A498 renal cancer cell line. Compound 2l was tested over a panel of 20 kinases to determine its molecular target(s), and its IC(50) values over the most sensitive kinases were defined. In vitro stability and in vivo pharmacokinetic profile of compound 2l was also investigated. Taylor & Francis 2018-10-26 /pmc/articles/PMC6211260/ /pubmed/30362383 http://dx.doi.org/10.1080/14756366.2018.1530225 Text en © 2018 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. http://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/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Paper Abdel-Maksoud, Mohammed S. El-Gamal, Mohammed I. Gamal El-Din, Mahmoud M. Oh, Chang Hyun Design, synthesis, in vitro anticancer evaluation, kinase inhibitory effects, and pharmacokinetic profile of new 1,3,4-triarylpyrazole derivatives possessing terminal sulfonamide moiety |
title | Design, synthesis, in vitro anticancer evaluation, kinase inhibitory effects, and pharmacokinetic profile of new 1,3,4-triarylpyrazole derivatives possessing terminal sulfonamide moiety |
title_full | Design, synthesis, in vitro anticancer evaluation, kinase inhibitory effects, and pharmacokinetic profile of new 1,3,4-triarylpyrazole derivatives possessing terminal sulfonamide moiety |
title_fullStr | Design, synthesis, in vitro anticancer evaluation, kinase inhibitory effects, and pharmacokinetic profile of new 1,3,4-triarylpyrazole derivatives possessing terminal sulfonamide moiety |
title_full_unstemmed | Design, synthesis, in vitro anticancer evaluation, kinase inhibitory effects, and pharmacokinetic profile of new 1,3,4-triarylpyrazole derivatives possessing terminal sulfonamide moiety |
title_short | Design, synthesis, in vitro anticancer evaluation, kinase inhibitory effects, and pharmacokinetic profile of new 1,3,4-triarylpyrazole derivatives possessing terminal sulfonamide moiety |
title_sort | design, synthesis, in vitro anticancer evaluation, kinase inhibitory effects, and pharmacokinetic profile of new 1,3,4-triarylpyrazole derivatives possessing terminal sulfonamide moiety |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6211260/ https://www.ncbi.nlm.nih.gov/pubmed/30362383 http://dx.doi.org/10.1080/14756366.2018.1530225 |
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