Synthesis of halogenated flavonoids as anti-dengue agents

Abstract

Flavonoids have been recognized as promising compounds with various bioactivities. Certain flavonoid derivatives exhibited more potent activities than their parent compounds. Recently, halogenated flavonoids have been addressed for their anti-dengue activity. In this research, a series of twenty-two brominated and iodinated flavonoid derivatives were synthesized and explored for dengue infection inhibition. Seventeen derivatives have been investigated for the first time. 8-Bromobaicalein, 6,8-dibromopinocembrin, 6,8-dibromopinostrobin, 6,8-diiodopinostrobin were disclosed as effective and non-toxic anti-dengue agents. These compounds displayed remarkably low EC50 as well as high CC50, which could be considered as potent therapeutic agents. Moreover, the preliminary screening on brominated O7-ether chrysins discovered some noticeable compounds, for example, 6,8-dibromo-O7-butylchrysin and 6,8-dibromo-O7-hexylchrysin; nonetheless, some synthesized brominated O7-ether chrysins were insoluble under tested conditions. Though the relationship between the length of side chain and bioactivity were inconsistent, there was a gradually increasing in percentage of plaque inhibition from ethyl to hexyl in case of 6,8-dibromo O7-ether chrysins.