Abstract
A novel series of 3-acetamido-4-methyl benzoic acid derivatives designed on the basis of vHTS hit ZINC02765569 were synthesized and screened for PTP1B inhibitory activity. The most potent compounds 3-(1-(5-methoxy-1H-benzo[d]imidazol-2-ylthio)acetamido)-4-methyl benzoic acid (10c, IC₅₀ 8.2 μM) and 3-(2-(benzo[d]thiazol-2-ylthio)acetamido)-4-methyl benzoic acid (10e, IC₅₀ 8.3 μM) showed maximum PTP1B inhibitory activity. Docking studies were also performed to understand the nature of interactions governing the binding mode of the designed molecules within the active site of the PTP1B enzyme.
Keywords:
Acetamido benzoic acid derivatives; Diabetes; Lead optimization; Molecular modelling; PTP1B.
Copyright © 2013 Elsevier Masson SAS. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetamides / chemical synthesis
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Acetamides / chemistry
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Acetamides / pharmacology*
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Antineoplastic Agents / chemical synthesis
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology*
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Benzoates / chemical synthesis
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Benzoates / chemistry
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Benzoates / pharmacology*
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Dose-Response Relationship, Drug
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Drug Design*
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Drug Screening Assays, Antitumor
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Enzyme Inhibitors / chemical synthesis
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology*
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Humans
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MCF-7 Cells
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Models, Molecular
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Molecular Structure
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Protein Tyrosine Phosphatase, Non-Receptor Type 1 / antagonists & inhibitors*
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Protein Tyrosine Phosphatase, Non-Receptor Type 1 / metabolism
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Structure-Activity Relationship
Substances
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3-acetamido-4-methyl benzoic acid
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Acetamides
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Antineoplastic Agents
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Benzoates
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Enzyme Inhibitors
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Protein Tyrosine Phosphatase, Non-Receptor Type 1