Synthesis of Polymethoxylated 3-Styrylflavones and their Antiproliferative Activity in HL60 Cells

Flavonoids are a large group of naturally occurring compounds with a wide range of biological properties and thus they represent a privileged scaffold in medicinal chemistry. We designed and synthesized a series of polymethoxylated 3-styrylflavones as a novel class of styryl-bearing flavone compounds.

3-Styrylflavones were systematically synthesized using Wittig reaction between various benzaldehyde derivatives and polymethoxylated 3-(bromomethyl)flavones, and evaluated their antiproliferative activity against HL60.

Among the compounds synthesized, 2',3',4'-trimethoxy-3-(E)-styrylflavone (IC₅₀=68 μM) and 2',3',3‴,4',4‴,5‴-hexamethoxy-3-(E)-styrylflavone (IC₅₀=92 μM) demonstrated potent anti-proliferative activity.

Introduction of 3-styryl substituent in 3-methylflavone increased the antiproliferative activity. Structure-activity relationship studies and theoretical calculations indicated the importance of 2',3',4'-trimethoxy-phenyl substituent in enhancing the activity.