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Novel Cruzain Inhibitors for the Treatment of Chagas’ Disease
Author(s) -
Rogers Kathleen E,
Keränen Henrik,
Durrant Jacob D.,
Ratnam Joseline,
Doak Allison,
Arkin Michelle R.,
McCammon J. Andrew
Publication year - 2012
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/j.1747-0285.2012.01416.x
Subject(s) - chagas disease , trypanosoma cruzi , disease , cysteine protease , medicine , pharmacology , biology , protease , immunology , computer science , parasite hosting , biochemistry , pathology , enzyme , world wide web
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.