Structure-activity relationship of dibenzylideneacetone analogs against the neglected disease pathogen, Trypanosoma brucei.

ABSTRACT: Trypanosoma brucei is a protozoan parasite that causes Human African Trypanosomiasis (HAT), a neglected tropical disease (NTD) that is endemic in 36 countries in sub-Saharan Africa. Only a handful drugs are available for treatment, and these have limitations, including toxicity and drug resistance. Using the natural product, curcumin, as a starting point, several curcuminoids and related analogs were evaluated against bloodstream forms of T. b. brucei. A particular subset of dibenzylideneacetone (DBA) compounds exhibited potent in vitro antitrypanosomal activity with sub-micromolar EC₅₀ values. A structure-activity relationship study including 26 DBA analogs was initiated, and several compounds exhibited EC₅₀ values as low as 200 nM. Cytotoxicity counter screens in HEK293 cells identified several compounds having selectivity indices above 10. These data suggest that DBAs offer starting points for a new small molecule therapy of HAT.

SUBMITTER: Francisco KR 

PROVIDER: S-EPMC10072319 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature