Synthesis And Structure Activity Relationships Of Anti-Trypanosomal Aurone-Based Compounds

Aurones, discovered over seventy years ago, are a class of molecules belonging to the flavonoids family of natural products. Perhaps the most notable aurone from plants is aureusidin, extracted from the snapdragon. Due to the discovery that some aurone derivatives can serve as potent biological agents and the ease through which they can be accessed synthetically, interest in aurone derivatives has increased in recent years. A library of aurone derivatives was synthesized to probe the aurone scaffold against in vitro models for trypanosomal diseases. The library incorporates a wide range of functionality including bioisosteres and exploration of different levels of lipophilicity. Structure activity relationships were evaluated to guide further optimization of these compounds to treat trypanosomal diseases. When compared with the basic, unsubstituted aurone scaffold, 53% of the synthetic derivatives produced greater inhibition of Trypanosoma brucei and 28% had selectivity multiples (parasite/toxicity) > 10.