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Synthesis, Molecular Docking Analysis, and Biological Evaluations of Saccharide-Modified Sulfonamides as Carbonic Anhydrase IX Inhibitors
Based on the strategy of the “tail approach”, 15 novel saccharide-modified sulfonamides were designed and synthesised. The novel compounds were evaluated as inhibitors of three human carbonic anhydrase (CA) isoforms, namely cytoplasmic CA II, transmembrane CA IX, and XII. Most of these compounds sho...
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/PMC8704611/ https://www.ncbi.nlm.nih.gov/pubmed/34948406 http://dx.doi.org/10.3390/ijms222413610 |
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author | Zhang, Zuopeng Yang, Huali Zhong, Ye Wang, Yueqing Wang, Jian Cheng, Maosheng Liu, Yang |
author_facet | Zhang, Zuopeng Yang, Huali Zhong, Ye Wang, Yueqing Wang, Jian Cheng, Maosheng Liu, Yang |
author_sort | Zhang, Zuopeng |
collection | PubMed |
description | Based on the strategy of the “tail approach”, 15 novel saccharide-modified sulfonamides were designed and synthesised. The novel compounds were evaluated as inhibitors of three human carbonic anhydrase (CA) isoforms, namely cytoplasmic CA II, transmembrane CA IX, and XII. Most of these compounds showed good activity against CAs and high topological polar surface area (TPSA) values, which had a positive effect on the selective inhibition of transmembrane isoforms CA IX and XII. In the in vitro activity studies, compounds 16a, 16b, and 16e reduced the viability of HT-29 and MDA-MB-231 cells with a high expression of CA IX under hypoxia. The inhibitory activity of compound 16e on the human osteosarcoma cell line MG-63 with a high expression of CA IX and XII was better than that of AZM. Moreover, high concentrations of compounds 16a and 16b reversed the acidification of the tumour microenvironment. In addition, compound 16a had a certain inhibitory effect on the migration of MDA-MB-231 cells. All the above results indicate that the saccharide-modified sulfonamide has further research value for the development of CA IX inhibitors. |
format | Online Article Text |
id | pubmed-8704611 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-87046112021-12-25 Synthesis, Molecular Docking Analysis, and Biological Evaluations of Saccharide-Modified Sulfonamides as Carbonic Anhydrase IX Inhibitors Zhang, Zuopeng Yang, Huali Zhong, Ye Wang, Yueqing Wang, Jian Cheng, Maosheng Liu, Yang Int J Mol Sci Article Based on the strategy of the “tail approach”, 15 novel saccharide-modified sulfonamides were designed and synthesised. The novel compounds were evaluated as inhibitors of three human carbonic anhydrase (CA) isoforms, namely cytoplasmic CA II, transmembrane CA IX, and XII. Most of these compounds showed good activity against CAs and high topological polar surface area (TPSA) values, which had a positive effect on the selective inhibition of transmembrane isoforms CA IX and XII. In the in vitro activity studies, compounds 16a, 16b, and 16e reduced the viability of HT-29 and MDA-MB-231 cells with a high expression of CA IX under hypoxia. The inhibitory activity of compound 16e on the human osteosarcoma cell line MG-63 with a high expression of CA IX and XII was better than that of AZM. Moreover, high concentrations of compounds 16a and 16b reversed the acidification of the tumour microenvironment. In addition, compound 16a had a certain inhibitory effect on the migration of MDA-MB-231 cells. All the above results indicate that the saccharide-modified sulfonamide has further research value for the development of CA IX inhibitors. MDPI 2021-12-19 /pmc/articles/PMC8704611/ /pubmed/34948406 http://dx.doi.org/10.3390/ijms222413610 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 Zhang, Zuopeng Yang, Huali Zhong, Ye Wang, Yueqing Wang, Jian Cheng, Maosheng Liu, Yang Synthesis, Molecular Docking Analysis, and Biological Evaluations of Saccharide-Modified Sulfonamides as Carbonic Anhydrase IX Inhibitors |
title | Synthesis, Molecular Docking Analysis, and Biological Evaluations of Saccharide-Modified Sulfonamides as Carbonic Anhydrase IX Inhibitors |
title_full | Synthesis, Molecular Docking Analysis, and Biological Evaluations of Saccharide-Modified Sulfonamides as Carbonic Anhydrase IX Inhibitors |
title_fullStr | Synthesis, Molecular Docking Analysis, and Biological Evaluations of Saccharide-Modified Sulfonamides as Carbonic Anhydrase IX Inhibitors |
title_full_unstemmed | Synthesis, Molecular Docking Analysis, and Biological Evaluations of Saccharide-Modified Sulfonamides as Carbonic Anhydrase IX Inhibitors |
title_short | Synthesis, Molecular Docking Analysis, and Biological Evaluations of Saccharide-Modified Sulfonamides as Carbonic Anhydrase IX Inhibitors |
title_sort | synthesis, molecular docking analysis, and biological evaluations of saccharide-modified sulfonamides as carbonic anhydrase ix inhibitors |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8704611/ https://www.ncbi.nlm.nih.gov/pubmed/34948406 http://dx.doi.org/10.3390/ijms222413610 |
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