Novel Cruzain Inhibitors for the Treatment of Chagas' Disease
2012 (English)In: Chemical Biology and Drug Design, ISSN 1747-0277, Vol. 80, no 3, 398-405 p.Article in journal (Refereed) Published
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.similar to 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.
Place, publisher, year, edition, pages
2012. Vol. 80, no 3, 398-405 p.
Chagas' disease, computer-aided drug discovery, cruzain, cruzipain, cysteine protease inhibitor, Trypanosoma cruzi
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-179897DOI: 10.1111/j.1747-0285.2012.01416.xISI: 000306664800007OAI: oai:DiVA.org:uu-179897DiVA: diva2:547535