Design, Synthesis and Biological Evaluation of a Library of Thiocarbazates and Their Activity as Cysteine Protease Inhibitors

Author(s): Zhuqing Liu, Michael C. Myers, Parag P. Shah, Mary Pat Beavers, Phillip A. Benedetti, Scott L. Diamond, Amos B. Smith,III, Donna M. Huryn.

Journal Name: Combinatorial Chemistry & High Throughput Screening

Volume 13 , Issue 4 , 2010

Become EABM
Become Reviewer


Recently, we identified a novel class of potent cathepsin L inhibitors, characterized by a thiocarbazate warhead. Given the potential of these compounds to inhibit other cysteine proteases, we designed and synthesized a library of thiocarbazates containing diversity elements at three positions. Biological characterization of this library for activity against a panel of proteases indicated a significant preference for members of the papain family of cysteine proteases over serine, metallo-, and certain classes of cysteine proteases, such as caspases. Several potent inhibitors of cathepsin L and S were identified. The SAR data were employed in docking studies in an effort to understand the structural elements required for cathepsin S inhibition. This study provides the basis for the design of highly potent and selective inhibitors of the papain family of cysteine proteases.

Keywords: Thiocarbazates, cathepsin B, cathepsin S, cathepsin L, cysteine protease inhibitor, library

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2010
Page: [337 - 351]
Pages: 15
DOI: 10.2174/138620710791054303
Price: $58

Article Metrics

PDF: 4