Abstract
A series of secondary and tertiary aryl sulfonamides were synthesized under flow conditions and evaluated for their ability to selectively inhibit tumor-associated carbonic anhydrase isoforms IX and XII. The tested compounds revealed to be highly potent CA IX inhibitors in nanomolar range, and to inhibit CA XII activity with different ranks of potencies. Remarkably, 4-methyl-N-phenyl-benzenesulfonamide was a selective nanomolar CA IX inhibitor with an IC50 of 90 nM.
Keywords:
Carbonic anhydrases; Docking; Flow synthesis; Sulfonamides.
Copyright © 2014 Elsevier Ltd. All rights reserved.
MeSH terms
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Antigens, Neoplasm / metabolism*
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Carbonic Anhydrase IX
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Carbonic Anhydrase Inhibitors / chemical synthesis
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Carbonic Anhydrase Inhibitors / chemistry
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Carbonic Anhydrase Inhibitors / pharmacology*
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Carbonic Anhydrases / metabolism*
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Dose-Response Relationship, Drug
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Humans
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Models, Molecular
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Molecular Structure
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Structure-Activity Relationship
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Sulfonamides / chemical synthesis
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Sulfonamides / chemistry
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Sulfonamides / pharmacology*
Substances
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Antigens, Neoplasm
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Carbonic Anhydrase Inhibitors
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Sulfonamides
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CA9 protein, human
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Carbonic Anhydrase IX
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Carbonic Anhydrases
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carbonic anhydrase XII