![]() ![]() Human African trypanosomiasis (HAT), or African sleeping sickness, is endemic in sub-Saharan Africa, claiming the lives of about 10 000 people every year. Further work is required to increase selectivity over the human NMT isoform and activity against T. A series of trypanocidal compounds were identified with suitable in vitro DMPK properties, including CNS exposure for further development. Using an X-ray crystallography/structure-based design approach, the benzomorpholinone series was further optimised, increasing activity against T. The benzomorpholinone was also found to bind in a similar region. This provides potential for further optimisation. An X-ray crystal structure of the thiazolidinone hit in Leishmania major NMT showed the compound bound in the previously reported active site, utilising a novel binding mode. ![]() ![]() Herein we describe work around thiazolidinone and benzomorpholine scaffolds that were also identified in the screen. We previously reported the development of some very potent compounds based around a pyrazole sulfonamide series, derived from a high-throughput screen. The enzyme N-myristoyltransferase (NMT) from Trypanosoma brucei has been validated both chemically and biologically as a potential drug target for human African trypanosomiasis. ![]()
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |