Abstract
Various N-sulfonylamino acid derivatives were synthesized and evaluated for their in vitro and in vivo activities to inhibit type IV collagenase (MMP-9 and MMP-2). When the amino acid residue and the sulfonamide moiety were modified, their inhibitory activities were greatly affected by the structure of the sulfonamide moiety. A series of aryl sulfonamide derivatives containing biaryl, tetrazole, amide, and triple bond were found to be potent and highly selective inhibitors of MMP-9 and MMP-2. In addition, these compounds were orally active in animal models of tumor growth and metastasis. These results revealed the potential of the N-sulfonylamino acid derivatives as a new type of candidate drug for the treatment of cancer.
MeSH terms
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Administration, Oral
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Animals
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Antineoplastic Agents / chemical synthesis*
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacokinetics
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Antineoplastic Agents / toxicity
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Gelatinases / antagonists & inhibitors*
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Humans
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Indicators and Reagents
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Kinetics
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Lung Neoplasms / drug therapy*
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Lung Neoplasms / pathology
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Matrix Metalloproteinase 2
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Metalloendopeptidases / antagonists & inhibitors*
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Mice
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Mice, Nude
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Molecular Structure
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Protease Inhibitors / chemical synthesis*
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Protease Inhibitors / chemistry
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Protease Inhibitors / pharmacokinetics
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Protease Inhibitors / pharmacology
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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 / pharmacokinetics
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Sulfonamides / pharmacology
Substances
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Antineoplastic Agents
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Indicators and Reagents
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Protease Inhibitors
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Sulfonamides
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Gelatinases
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Metalloendopeptidases
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Matrix Metalloproteinase 2