Abstract
Human carbonic anhydrases IX and XII are upregulated in many tumors and form a novel target for new generation anticancer drugs. Here we report the synthesis of novel 2-indolinone derivatives with the sulfonamide group as a zinc binding moiety. Enzyme inhibition assays confirmed that the compounds showed selectivity against hCA IX and XII over the widely distributed off-targets hCA I and II. Molecular modelling studies were performed to suggest modes of binding for these compounds.
Keywords:
2-Indolinone; Carbonic anhydrase; Docking; Isatin.
Copyright © 2017 Elsevier Ltd. All rights reserved.
MeSH terms
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Antineoplastic Agents / chemical synthesis
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Antineoplastic Agents / chemistry*
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Antineoplastic Agents / metabolism
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Binding Sites
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Carbonic Anhydrase I / antagonists & inhibitors
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Carbonic Anhydrase I / metabolism
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Carbonic Anhydrase II / antagonists & inhibitors
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Carbonic Anhydrase II / metabolism
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Carbonic Anhydrase IX / antagonists & inhibitors
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Carbonic Anhydrase IX / metabolism
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Carbonic Anhydrase Inhibitors / chemical synthesis
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Carbonic Anhydrase Inhibitors / chemistry*
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Carbonic Anhydrase Inhibitors / metabolism
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Carbonic Anhydrases / chemistry*
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Carbonic Anhydrases / metabolism
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Catalytic Domain
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Humans
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Indoles / chemical synthesis
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Indoles / chemistry*
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Indoles / metabolism
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Inhibitory Concentration 50
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Molecular Docking Simulation
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Oxindoles
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Structure-Activity Relationship
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Sulfonamides / chemistry*
Substances
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Antineoplastic Agents
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Carbonic Anhydrase Inhibitors
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Indoles
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Oxindoles
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Sulfonamides
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2-oxindole
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Carbonic Anhydrase I
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Carbonic Anhydrase II
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Carbonic Anhydrase IX
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Carbonic Anhydrases
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carbonic anhydrase XII