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

作者：Kumar G D Kishore; Chavarria Gustavo E; Charlton Sevcik Amanda K; Arispe Wara M; MacDonough Matthew T; Strecker Tracy E; Chen Shen En; Siim Bronwyn G; Chaplin David J; Trawick Mary Lynn; Pinney Kevin G^*

来源：Bioorganic & Medicinal Chemistry Letters, 2010, 20(4): 1415-1419.

DOI：10.1016/j.bmcl.2009.12.090

• Inhibitors of cathepsin L
• Inhibitors of cathepsin B
• Chemical synthesis
• Molecular design
• Molecular modeling

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 (IC(50) < 85 nM) in this series incorporate a meta-bromo sub-stituent 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 (IC(50) > 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.

• 出版日期2010-2-15