Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhang, Zuopeng, Yang, Huali, Zhong, Ye, Wang, Yueqing, Wang, Jian, Cheng, Maosheng, Liu, Yang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
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
_version_ 1784621748249952256
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
work_keys_str_mv AT zhangzuopeng synthesismoleculardockinganalysisandbiologicalevaluationsofsaccharidemodifiedsulfonamidesascarbonicanhydraseixinhibitors
AT yanghuali synthesismoleculardockinganalysisandbiologicalevaluationsofsaccharidemodifiedsulfonamidesascarbonicanhydraseixinhibitors
AT zhongye synthesismoleculardockinganalysisandbiologicalevaluationsofsaccharidemodifiedsulfonamidesascarbonicanhydraseixinhibitors
AT wangyueqing synthesismoleculardockinganalysisandbiologicalevaluationsofsaccharidemodifiedsulfonamidesascarbonicanhydraseixinhibitors
AT wangjian synthesismoleculardockinganalysisandbiologicalevaluationsofsaccharidemodifiedsulfonamidesascarbonicanhydraseixinhibitors
AT chengmaosheng synthesismoleculardockinganalysisandbiologicalevaluationsofsaccharidemodifiedsulfonamidesascarbonicanhydraseixinhibitors
AT liuyang synthesismoleculardockinganalysisandbiologicalevaluationsofsaccharidemodifiedsulfonamidesascarbonicanhydraseixinhibitors