Development of cell-active non-peptidyl inhibitors of cysteine cathepsins
| Autor: | Ranjith K. Gamage, Nisar Afzal, Sanjai Kumar, Anibal R. Davalos, Kevin J. Mark, Susan A. Rotenberg, Emmanuel J. Chang, Yuriy Zavlanov, Suneeta Paroly, Juliana Huestis, Shatarupa De, Gopal Subramaniam, Dibyendu Dana, Pratikkumar Rathod |
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| Rok vydání: | 2013 |
| Předmět: |
Clinical Biochemistry
Cell Pharmaceutical Science Cysteine Proteinase Inhibitors Biochemistry Structure-Activity Relationship Cell Movement Live cell imaging Cell Line Tumor Drug Discovery medicine Humans Structure–activity relationship Cysteine Sulfones Molecular Biology Cathepsin chemistry.chemical_classification Organic Chemistry Cathepsins Small molecule Molecular Docking Simulation Kinetics medicine.anatomical_structure Enzyme chemistry Cell culture Epoxy Compounds Thermodynamics Molecular Medicine |
| Zdroj: | Bioorganic & Medicinal Chemistry. 21:2975-2987 |
| ISSN: | 0968-0896 |
| DOI: | 10.1016/j.bmc.2013.03.062 |
| Popis: | Cysteine cathepsins are an important class of enzymes that coordinate a variety of important cellular processes, and are implicated in various types of human diseases. However, small molecule inhibitors that are cell-permeable and non-peptidyl in nature are scarcely available. Herein the synthesis and development of sulfonyloxiranes as covalent inhibitors of cysteine cathepsins are reported. From a library of compounds, compound 5 is identified as a selective inhibitor of cysteine cathepsins. Live cell imaging and immunocytochemistry of metastatic human breast carcinoma MDA-MB-231 cells document the efficacy of compound 5 in inhibiting cysteine cathepsin activity in living cells. A cell-motility assay demonstrates that compound 5 is effective in mitigating the cell-migratory potential of highly metastatic breast carcinoma MDA-MB-231 cells. |
| Databáze: | OpenAIRE |
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