Abstract
Hydrazide derivatives of Ilomastat, carrying either aryl groups or distinct alkyl and arylsulfonyl moieties were synthesized and evaluated for their MMP inhibitory activity. Potent and selective MMP-9 inhibition (IC(50)=3 nM) was observed for compound 3m (arylsulfonyl group: 4-(4-Br-C6H4)-C6H4-SO(2)-). Interaction with the S2 enzyme subsite is mainly responsible for the inhibitory properties of this derivative as confirmed by molecular docking computation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Algorithms
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Benzene / chemistry
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Benzene / pharmacology*
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Hydrazines / chemical synthesis
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Hydrazines / pharmacology*
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Hydroxamic Acids
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Indoles / chemical synthesis
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Indoles / pharmacology*
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Inhibitory Concentration 50
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Matrix Metalloproteinase Inhibitors*
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Models, Molecular
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Protease Inhibitors / chemical synthesis
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Protease Inhibitors / pharmacology*
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Structure-Activity Relationship
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Sulfonic Acids / chemistry
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Sulfonic Acids / pharmacology*
Substances
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Hydrazines
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Hydroxamic Acids
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Indoles
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Matrix Metalloproteinase Inhibitors
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Protease Inhibitors
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Sulfonic Acids
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ilomastat
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Benzene