TY - JOUR
T1 - Trypanothione reductase high-throughput screening campaign identifies novel classes of inhibitors with antiparasitic activity
AU - Holloway, Georgina A
AU - Charman, William Neil
AU - Fairlamb, Alan H
AU - Brun, Reto
AU - Kaiser, Marcel
AU - Kostewicz, Edmund Stanley
AU - Novello, Patrizia M
AU - Parisot, John P
AU - Richardson, John
AU - Street, Ian Philip
AU - Watson, Keith Geoffrey
AU - Baell, Jonathan B
PY - 2009
Y1 - 2009
N2 - High-throughput screening of 100,000 lead-like compounds led to the identification of nine novel chemical classes of trypanothione reductase (TR) inhibitors worthy of further investigation. Hits from five of these chemical classes have been developed further through different combinations of preliminary structure-activity relationship rate probing and assessment of antiparasitic activity, cytoxicity, and chemical and in vitro metabolic properties. This has led to the identification of novel TR inhibitor chemotypes that are drug-like and display antiparasitic activity. This paper explores the process of identifying, investigating, and evaluating a series of hits from a high-throughput screening campaign.
AB - High-throughput screening of 100,000 lead-like compounds led to the identification of nine novel chemical classes of trypanothione reductase (TR) inhibitors worthy of further investigation. Hits from five of these chemical classes have been developed further through different combinations of preliminary structure-activity relationship rate probing and assessment of antiparasitic activity, cytoxicity, and chemical and in vitro metabolic properties. This has led to the identification of novel TR inhibitor chemotypes that are drug-like and display antiparasitic activity. This paper explores the process of identifying, investigating, and evaluating a series of hits from a high-throughput screening campaign.
U2 - 10.1128/AAC.01568-08
DO - 10.1128/AAC.01568-08
M3 - Article
VL - 53
SP - 2824
EP - 2833
JO - Antimicrobial Agents and Chemotherapy
JF - Antimicrobial Agents and Chemotherapy
SN - 0066-4804
IS - 7
ER -