SAR Studies and Biological Characterization of a Chromen-4-one Derivative as an Anti- Agent.

Chemical modulation of the flavonol 2-(benzo[d][1,3]dioxol-5-yl)-chromen-4-one (), a promising anti-Trypanosomatid agent previously identified, was evaluated through a phenotypic screening approach. Herein, we have performed structure-activity relationship studies around hit compound . The pivaloyl derivative () showed significant anti- activity (EC = 1.1 μM) together with a selectivity index higher than 92. The early ADME-tox properties (cytotoxicity, mitochondrial toxicity, cytochrome P450 and ERG inhibition) were determined for compound and its derivatives, and these led to the identification of some liabilities. The 1,3-benzodioxole moiety in the presented compounds confers better in vivo pharmacokinetic properties than those of classical flavonols. Further studies using different delivery systems could lead to an increase of compound blood levels.