Development of cell-active non-peptidyl inhibitors of cysteine cathepsins

Dibyendu Dana, Anibal R. Davalos, Shatarupa De, Pratikkumar Rathod, Ranjith K. Gamage, Juliana Huestis, Nisar Afzal, Yuriy Zavlanov, Suneeta S. Paroly, Susan A. Rotenberg, Gopal Subramaniam, Kevin J. Mark, Emmanuel J. Chang, Sanjai Kumar

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)2975-2987
Number of pages13
JournalBioorganic and Medicinal Chemistry
Issue number11
StatePublished - Jun 1 2013

Bibliographical note

Funding Information:
The authors wish to gratefully acknowledge the funding support provided by the PSC-CUNY Research Award Program , and Queensborough Community College (QCC)/Queens College NSF-STEP and NIH Bridges programs .


  • Cancer metastasis
  • Cathepsin inhibitor
  • Cell migration
  • Cysteine protease inhibitor
  • Sulfonyloxiranes


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