Design,synthesis, and biological evaluation of potent thiosemicarbazone based cathepsin L inhibitors |
| |
Authors: | GD Kishore Kumar Gustavo E Chavarria Amanda K Charlton-Sevcik Wara M Arispe Matthew T MacDonough Tracy E Strecker Shen-En Chen Bronwyn G Siim David J Chaplin Mary Lynn Trawick Kevin G Pinney |
| |
Institution: | 1. Department of Chemistry and Biochemistry, Baylor University, One Bear Place #97348, Waco, TX 76798-7348, USA;2. OXiGENE Inc., Magdalen Center, Robert Robinson Avenue, The Oxford Science Park, OX4 4GA, UK |
| |
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. |
| |
Keywords: | |
本文献已被 ScienceDirect 等数据库收录! |
|