TY - JOUR
T1 - High-throughput screening affords novel and selective trypanothione reductase inhibitors with anti-trypanosomal activity
AU - Martyn, Derek C.
AU - Jones, Deuan C.
AU - Fairlamb, Alan H.
AU - Clardy, Jon
N1 - Funding Information:
Financial support was provided by the Drugs for Neglected Diseases Initiative (DNDi). A.H.F. is a Wellcome Trust Principal Research Fellow. We thank the National Cancer Institute’s Initiative for Chemical Genetics (contract no. N01-CO-12400), who provided support for this publication, and the Chemical Biology Platform of the Broad Institute of Harvard and MIT for their assistance in this work.
PY - 2007/3/1
Y1 - 2007/3/1
N2 - Trypanothione reductase (TR), an enzyme that buffers oxidative stress in trypanosomatid parasites, was screened against commercial libraries containing approximately 134,500 compounds. After secondary screening, four chemotypes were identified as screening positives with selectivity for TR over human glutathione reductase. Thirteen compounds from these four chemotypes were purchased, and their in vitro activity against TR and Trypanosoma brucei is described.
AB - Trypanothione reductase (TR), an enzyme that buffers oxidative stress in trypanosomatid parasites, was screened against commercial libraries containing approximately 134,500 compounds. After secondary screening, four chemotypes were identified as screening positives with selectivity for TR over human glutathione reductase. Thirteen compounds from these four chemotypes were purchased, and their in vitro activity against TR and Trypanosoma brucei is described.
KW - High-throughput screening
KW - Trypanosomiasis
KW - Trypanothione reductase
UR - http://www.scopus.com/inward/record.url?scp=33846933089&partnerID=8YFLogxK
U2 - 10.1016/j.bmcl.2006.12.016
DO - 10.1016/j.bmcl.2006.12.016
M3 - Article
C2 - 17197182
AN - SCOPUS:33846933089
SN - 0960-894X
VL - 17
SP - 1280
EP - 1283
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
IS - 5
ER -