Synthesis, Molecular Docking Analysis and Biological Evaluations of Saccharide-Modified Thiadiazole Sulfonamide Derivatives

A series of saccharide-modified thiadiazole sulfonamide derivatives has been designed and synthesized by the “tail approach” and evaluated for inhibitory activity against carbonic anhydrases II, IX, and XII. Most of the compounds showed high topological polar surface area (TPSA) values and excellent...

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Main Authors: Zuo-Peng Zhang, Ye Zhong, Zhen-Bin Han, Lin Zhou, Hua-Sheng Su, Jian Wang, Yang Liu, Mao-Sheng Cheng
Format: Article
Language:English
Published: MDPI AG 2021-05-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/22/11/5482
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author Zuo-Peng Zhang
Ye Zhong
Zhen-Bin Han
Lin Zhou
Hua-Sheng Su
Jian Wang
Yang Liu
Mao-Sheng Cheng
author_facet Zuo-Peng Zhang
Ye Zhong
Zhen-Bin Han
Lin Zhou
Hua-Sheng Su
Jian Wang
Yang Liu
Mao-Sheng Cheng
author_sort Zuo-Peng Zhang
collection DOAJ
description A series of saccharide-modified thiadiazole sulfonamide derivatives has been designed and synthesized by the “tail approach” and evaluated for inhibitory activity against carbonic anhydrases II, IX, and XII. Most of the compounds showed high topological polar surface area (TPSA) values and excellent enzyme inhibitory activity. The impacts of some compounds on the viability of HT-29, MDA-MB-231, and MG-63 human cancer cell lines were examined under both normoxic and hypoxic conditions, and they showed certain inhibitory effects on cell viability. Moreover, it was found that the series of compounds had the ability to raise the pH of the tumor cell microenvironment. All the results proved that saccharide-modified thiadiazole sulfonamides have important research prospects for the development of CA IX inhibitors.
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spelling doaj.art-0fa2a3c23ae5487c89c58e41c61bc9ab2023-11-21T20:57:23ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-05-012211548210.3390/ijms22115482Synthesis, Molecular Docking Analysis and Biological Evaluations of Saccharide-Modified Thiadiazole Sulfonamide DerivativesZuo-Peng Zhang0Ye Zhong1Zhen-Bin Han2Lin Zhou3Hua-Sheng Su4Jian Wang5Yang Liu6Mao-Sheng Cheng7Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, ChinaKey Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, ChinaKey Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, ChinaKey Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, ChinaKey Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, ChinaKey Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, ChinaKey Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, ChinaKey Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, ChinaA series of saccharide-modified thiadiazole sulfonamide derivatives has been designed and synthesized by the “tail approach” and evaluated for inhibitory activity against carbonic anhydrases II, IX, and XII. Most of the compounds showed high topological polar surface area (TPSA) values and excellent enzyme inhibitory activity. The impacts of some compounds on the viability of HT-29, MDA-MB-231, and MG-63 human cancer cell lines were examined under both normoxic and hypoxic conditions, and they showed certain inhibitory effects on cell viability. Moreover, it was found that the series of compounds had the ability to raise the pH of the tumor cell microenvironment. All the results proved that saccharide-modified thiadiazole sulfonamides have important research prospects for the development of CA IX inhibitors.https://www.mdpi.com/1422-0067/22/11/5482saccharidetail approachpH of the tumor cell microenvironmentCA IX inhibitors
spellingShingle Zuo-Peng Zhang
Ye Zhong
Zhen-Bin Han
Lin Zhou
Hua-Sheng Su
Jian Wang
Yang Liu
Mao-Sheng Cheng
Synthesis, Molecular Docking Analysis and Biological Evaluations of Saccharide-Modified Thiadiazole Sulfonamide Derivatives
International Journal of Molecular Sciences
saccharide
tail approach
pH of the tumor cell microenvironment
CA IX inhibitors
title Synthesis, Molecular Docking Analysis and Biological Evaluations of Saccharide-Modified Thiadiazole Sulfonamide Derivatives
title_full Synthesis, Molecular Docking Analysis and Biological Evaluations of Saccharide-Modified Thiadiazole Sulfonamide Derivatives
title_fullStr Synthesis, Molecular Docking Analysis and Biological Evaluations of Saccharide-Modified Thiadiazole Sulfonamide Derivatives
title_full_unstemmed Synthesis, Molecular Docking Analysis and Biological Evaluations of Saccharide-Modified Thiadiazole Sulfonamide Derivatives
title_short Synthesis, Molecular Docking Analysis and Biological Evaluations of Saccharide-Modified Thiadiazole Sulfonamide Derivatives
title_sort synthesis molecular docking analysis and biological evaluations of saccharide modified thiadiazole sulfonamide derivatives
topic saccharide
tail approach
pH of the tumor cell microenvironment
CA IX inhibitors
url https://www.mdpi.com/1422-0067/22/11/5482
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