Discovery of new S-adenosylmethionine decarboxylase inhibitors for the treatment of Human African Trypanosomiasis (HAT)

Modification of the structure of trypanosomal AdoMetDC inhibitor 1 (MDL73811) resulted in the identification of a new inhibitor 7a, which features a methyl substituent at the 8-position. Compound 7a exhibits improved potencies against both the trypanosomal AdoMetDC enzyme and parasites, and better blood brain barrier penetration than 1.

Graphical abstractCompound 7a, which has a methyl substituent at the 8-position of 5′-((Z)-4-aminobut-2-enyl)(methyl)amino)adenosine, demonstrates potent activity against the trypanosomal AdoMetDc enzyme and Trypanosoma brucei strains, and has an increased ability to penetrate the blood brain barrier.Figure optionsDownload full-size imageDownload as PowerPoint slide