Novel benzoyl thioureido benzene sulfonamides as highly potent and selective inhibitors of carbonic anhydrase IX: Optimization and bioactive studies

Li Liu; Wanqi Wang; Jin Huang; Zhenjiang Zhao; Honglin Li; Yufang Xu

doi:10.1039/c8md00392k

Novel benzoyl thioureido benzene sulfonamides as highly potent and selective inhibitors of carbonic anhydrase IX: Optimization and bioactive studies

Li Liu
, Wanqi Wang
, Jin Huang
, Zhenjiang Zhao
, Honglin Li^*
, Yufang Xu

^*Corresponding author for this work

East China University of Science and Technology

Research output: Contribution to journal › Article › peer-review

5 Scopus citations

Abstract

CA IX has attracted much attention as a promising target for the development of new anticancer agents. In this study, a series of sulfonamide derivatives were designed and synthesized as potential CA IX inhibitors from a lead compound (benzoyl thioureido benzene sulfonamide) discovered by virtual screening. The bioassay demonstrated that some of the synthesized compounds exhibited potent inhibitory activity against CA IX in the subnanomolar range and high selectivity over isozymes CA I and CA II. Among them, compound 6a displayed inhibitory activity against CA IX with an IC ₅₀ value of 0.48 nM and about 1500-fold selectivity over CA II. The structure-activity relationship and CA IX selectivity of the new sulfonamide derivatives were also analyzed by molecular docking.

Original language	English
Pages (from-to)	2100-2105
Number of pages	6
Journal	MedChemComm
Volume	9
Issue number	12
DOIs	https://doi.org/10.1039/c8md00392k
State	Published - 2018
Externally published	Yes

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title = "Novel benzoyl thioureido benzene sulfonamides as highly potent and selective inhibitors of carbonic anhydrase IX: Optimization and bioactive studies",

abstract = " CA IX has attracted much attention as a promising target for the development of new anticancer agents. In this study, a series of sulfonamide derivatives were designed and synthesized as potential CA IX inhibitors from a lead compound (benzoyl thioureido benzene sulfonamide) discovered by virtual screening. The bioassay demonstrated that some of the synthesized compounds exhibited potent inhibitory activity against CA IX in the subnanomolar range and high selectivity over isozymes CA I and CA II. Among them, compound 6a displayed inhibitory activity against CA IX with an IC 50 value of 0.48 nM and about 1500-fold selectivity over CA II. The structure-activity relationship and CA IX selectivity of the new sulfonamide derivatives were also analyzed by molecular docking.",

author = "Li Liu and Wanqi Wang and Jin Huang and Zhenjiang Zhao and Honglin Li and Yufang Xu",

note = "Publisher Copyright: {\textcopyright} 2018 The Royal Society of Chemistry.",

year = "2018",

doi = "10.1039/c8md00392k",

language = "英语",

volume = "9",

pages = "2100--2105",

journal = "MedChemComm",

issn = "2040-2503",

publisher = "Royal Society of Chemistry",

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}

TY - JOUR

T1 - Novel benzoyl thioureido benzene sulfonamides as highly potent and selective inhibitors of carbonic anhydrase IX

T2 - Optimization and bioactive studies

AU - Liu, Li

AU - Wang, Wanqi

AU - Huang, Jin

AU - Zhao, Zhenjiang

AU - Li, Honglin

AU - Xu, Yufang

PY - 2018

Y1 - 2018

N2 - CA IX has attracted much attention as a promising target for the development of new anticancer agents. In this study, a series of sulfonamide derivatives were designed and synthesized as potential CA IX inhibitors from a lead compound (benzoyl thioureido benzene sulfonamide) discovered by virtual screening. The bioassay demonstrated that some of the synthesized compounds exhibited potent inhibitory activity against CA IX in the subnanomolar range and high selectivity over isozymes CA I and CA II. Among them, compound 6a displayed inhibitory activity against CA IX with an IC 50 value of 0.48 nM and about 1500-fold selectivity over CA II. The structure-activity relationship and CA IX selectivity of the new sulfonamide derivatives were also analyzed by molecular docking.

AB - CA IX has attracted much attention as a promising target for the development of new anticancer agents. In this study, a series of sulfonamide derivatives were designed and synthesized as potential CA IX inhibitors from a lead compound (benzoyl thioureido benzene sulfonamide) discovered by virtual screening. The bioassay demonstrated that some of the synthesized compounds exhibited potent inhibitory activity against CA IX in the subnanomolar range and high selectivity over isozymes CA I and CA II. Among them, compound 6a displayed inhibitory activity against CA IX with an IC 50 value of 0.48 nM and about 1500-fold selectivity over CA II. The structure-activity relationship and CA IX selectivity of the new sulfonamide derivatives were also analyzed by molecular docking.

UR - https://www.scopus.com/pages/publications/85058626163

U2 - 10.1039/c8md00392k

DO - 10.1039/c8md00392k

M3 - 文章

AN - SCOPUS:85058626163

SN - 2040-2503

VL - 9

SP - 2100

EP - 2105

JO - MedChemComm

JF - MedChemComm

IS - 12

ER -

Novel benzoyl thioureido benzene sulfonamides as highly potent and selective inhibitors of carbonic anhydrase IX: Optimization and bioactive studies

Abstract

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