Design, synthesis, and biological evaluation of potent thiosemicarbazone based cathepsin L inhibitors

Kumar, G.D.K. et al. (2010) Design, synthesis, and biological evaluation of potent thiosemicarbazone based cathepsin L inhibitors. Bioorganic and Medicinal Chemistry Letters, 20(4), pp. 1415-1419. (doi: 10.1016/j.bmcl.2009.12.090)

Abstract

A small library of 36 functionalized benzophenone thiosemicarbazone analogs has been prepared by chemical synthesis and evaluated for their ability to inhibit the cysteine proteases cathepsin L and cathepsin B. Inhibitors of cathepsins L and B have the potential to limit or arrest cancer metastasis. The six most active inhibitors of cathepsin L (IC₅₀ < 85 nM) in this series incorporate a meta-bromo substituent in one aryl ring along with a variety of functional groups in the second aryl ring. These six analogs are selective for their inhibition of cathepsin L versus cathepsin B (IC₅₀ > 10,000 nM). The most active analog in the series, 3-bromophenyl-2′-fluorophenyl thiosemicarbazone 1, also efficiently inhibits cell invasion of the DU-145 human prostate cancer cell line.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Gaddale Devanna, Dr Kishore Kumar
• Authors: Kumar, G.D.K., Chavarria, G.E., Charlton-Sevcik, A.K., Arispe, W.M., MacDonough, M.T., Strecker, T.E., Chen, S.E., Siim, B.G.., Chaplin, D.J., Trawick, M.L., and Pinney, K.G.
• College/School: College of Science and Engineering > School of Chemistry
• Journal Name: Bioorganic and Medicinal Chemistry Letters
• ISSN: 0960-894X
• ISSN (Online): 1464-3405