s-3304 and Lung-Neoplasms

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.

Topics: Administration, Oral; Animals; Antineoplastic Agents; Gelatinases; Humans; Indicators and Reagents; Kinetics; Lung Neoplasms; Matrix Metalloproteinase 2; Metalloendopeptidases; Mice; Mice, Nude; Molecular Structure; Protease Inhibitors; Structure-Activity Relationship; Sulfonamides