The trans-sialidase protein expressed by Trypanosoma cruzi is an important enzyme in the life cycle of this human pathogenic parasite and is considered a promising target for the development of new drug treatments against Chagas' disease. Here we describe α-amino phosphonates as a novel class of inhibitor of T. cruzi trans-sialidase. Molecular modelling studies were initially used to predict the active-site binding affinities for a series of amino phosphonates, which were subsequently synthesised and their IC 50s determined in vitro. The measured inhibitory activities show some correlation with the predictions from molecular modelling, with 1-napthyl derivatives found to be the most potent inhibitors having IC 50s in the low micromolar range. Interestingly, kinetic analysis of the mode of inhibition demonstrated that the α-aminophosphonates tested here operate in a non-competitive manner.
- Trypanosoma cruzi
ASJC Scopus subject areas
- Drug Discovery
- Organic Chemistry
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- Department of Biology & Biochemistry - Professor
- Centre for Sustainable and Circular Technologies (CSCT)
- Centre for Therapeutic Innovation
- Centre for Biosensors, Bioelectronics and Biodevices (C3Bio)
- Centre for Integrated Bioprocessing Research (CIBR)
Person: Research & Teaching