Potent Arylsulfonamide Inhibitors of Tumor Necrosis Factor-α Converting Enzyme Able to Reduce Activated Leukocyte Cell Adhesion Molecule Shedding in Cancer Cell Models
Copyright policy )Potent Arylsulfonamide Inhibitors of Tumor Necrosis Factor-α Converting Enzyme Able to Reduce Activated Leukocyte Cell Adhesion Molecule Shedding in Cancer Cell Models
Activated leukocyte cell adhesion molecule (ALCAM) plays a relevant role in tumor biology and progression. Our previous studies showed that ALCAM is expressed at the surface of epithelial ovarian cancer (EOC) cells and is released in a soluble form by ADAM-17-mediated shedding. This process is relevant to EOC cell motility and invasiveness, which is reduced by nonspecific inhibitors of ADAM-17. For this reason, ADAM-17 may represent a new useful target in anticancer therapy. Herein, we report the synthesis and biological evaluation of new ADAM-17 inhibitors containing an arylsulfonamidic scaffold. Among the new potential inhibitors, two very promising compounds 17 and 18 were discovered, with a nanomolar activity for ADAM-17 isolated enzyme. These compounds proved to be also the most potent in inhibiting soluble ALCAM release in cancer cells, showing a nanomolar activity on A2774 and SKOV3 cell lines.
- University Federico II of Naples Italy
- University of Pisa Italy
Models, Molecular, Ovarian Neoplasms, Sulfonamides, Dose-Response Relationship, Drug, Molecular Structure, Blotting, Western, Enzyme-Linked Immunosorbent Assay, ADAM17 Protein, Hydroxamic Acids, ADAM Proteins, Kinetics, Structure-Activity Relationship, Models, Chemical, Activated-Leukocyte Cell Adhesion Molecule, Cell Line, Tumor, Humans, Female, Enzyme Inhibitors, Enzyme Assays, Protein Binding
Models, Molecular, Ovarian Neoplasms, Sulfonamides, Dose-Response Relationship, Drug, Molecular Structure, Blotting, Western, Enzyme-Linked Immunosorbent Assay, ADAM17 Protein, Hydroxamic Acids, ADAM Proteins, Kinetics, Structure-Activity Relationship, Models, Chemical, Activated-Leukocyte Cell Adhesion Molecule, Cell Line, Tumor, Humans, Female, Enzyme Inhibitors, Enzyme Assays, Protein Binding
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