Abstract:
:There is an urgent need for new drugs for the treatment of tropical parasitic diseases such as human African trypanosomiasis, which is caused by Trypanosoma brucei. The enzyme trypanothione reductase (TryR) is a potential drug target within these organisms. Herein we report the screening of a 62,000 compound library against T. brucei TryR. Further work was undertaken to optimise potency and selectivity of two novel-compound series arising from the enzymatic and whole parasite screens and mammalian cell counterscreens. Both of these series, containing either a quinoline or pyrimidinopyrazine scaffold, yielded low micromolar inhibitors of the enzyme and growth of the parasite. The challenges of inhibiting TryR with druglike molecules is discussed.
journal_name
ChemMedChemjournal_title
ChemMedChemauthors
Spinks D,Shanks EJ,Cleghorn LA,McElroy S,Jones D,James D,Fairlamb AH,Frearson JA,Wyatt PG,Gilbert IHdoi
10.1002/cmdc.200900262subject
Has Abstractpub_date
2009-12-01 00:00:00pages
2060-9issue
12eissn
1860-7179issn
1860-7187journal_volume
4pub_type
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