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Volume 21, Issue 2
  • ISSN: 1573-4064
  • E-ISSN: 1875-6638

Abstract

Introduction

Carbonic anhydrase IX (CAIX) is known to be overexpressed in various tumors and plays a significant role in tumor development and progression.

Methods

A series of 3-(benzylsulfonamido)benzamides derivatives was synthesized and tested for their CAIX inhibitory activities. The two most active compounds were subjected to cytotoxicity testing against a panel of 60 cancer cell lines.

Results

Many of the synthesized compounds successfully inhibited CAIX activities, exhibiting IC values in the low nanomolar range. The most potent CAIX inhibitor was compound , with an IC of 140 nM. Structure-activity relationship analysis of the synthesized compounds supported with molecular docking revealed strong coordination of sulfonamide moiety with the catalytic Zn2+ metal, hydrophobic interactions of the benzylsulfonamido ring with a hydrophobic pocket, and π-stacking interactions of the aryl ring with an aromatic surface. The two most active analogues ( and ) were further tested for their antiproliferative activities in the NCI-60 human tumor cell lines. Notably, compound demonstrated potent growth inhibitory effects against several cancer cell lines.

Conclusion

The synthesized analogues represent a novel scaffold for the treatment of different types of cancer by targeting CAIX.

© 2025 Bentham Science Publishers
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2025-05-23

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Design and Synthesis of 3-(Phenylsulfonamido)benzamide Derivatives as Potent Carbonic Anhydrase IX Inhibitors: Biological Evaluations and Molecular Modeling Studies
Med. Chem. 21, 160 (2025); https://doi.org/10.2174/0115734064325144240823073504
/content/journals/mc/10.2174/0115734064325144240823073504
/content/journals/mc/10.2174/0115734064325144240823073504
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  • Article Type:     Research Article
Keyword(s): cancer; Carbonic anhydrase; docking; NCI-60 human tumor; sulfonamide; synthesis

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