Novel Cruzain Inhibitors for the Treatment of Chagas’ Disease
Version of Record online: 27 JUN 2012
© 2012 John Wiley & Sons A/S
Chemical Biology & Drug Design
Volume 80, Issue 3, pages 398–405, September 2012
How to Cite
Rogers, K. E., Keränen, H., Durrant, J. D., Ratnam, J., Doak, A., Arkin, M. R. and McCammon, J. A. (2012), Novel Cruzain Inhibitors for the Treatment of Chagas’ Disease. Chemical Biology & Drug Design, 80: 398–405. doi: 10.1111/j.1747-0285.2012.01416.x
- Issue online: 23 JUL 2012
- Version of Record online: 27 JUN 2012
- Accepted manuscript online: 21 MAY 2012 07:22AM EST
- Received 14 March 2012, revised 28 April 2012 and accepted for publication 3 May 2012.
- Chagas’ disease;
- computer-aided drug discovery;
- cysteine protease inhibitor;
- Trypanosoma cruzi
The protozoan parasite Trypanosoma cruzi, the etiological agent of Chagas’ disease, affects millions of individuals and continues to be an important global health concern. The poor efficacy and unfavorable side effects of current treatments necessitate novel therapeutics. Cruzain, the major cysteine protease of T. cruzi, is one potential novel target. Recent advances in a class of vinyl sulfone inhibitors are encouraging; however, as most potential therapeutics fail in clinical trials and both disease progression and resistance call for combination therapy with several drugs, the identification of additional classes of inhibitory molecules is essential. Using an exhaustive virtual-screening and experimental validation approach, we identify several additional small-molecule cruzain inhibitors. Further optimization of these chemical scaffolds could lead to the development of novel drugs useful in the treatment of Chagas’ disease.