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

Abstract

Background/Aim: 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. Materials and Methods: 3-Styrylflavones were systematically synthesized using Wittig reaction between various benzaldehyde derivatives and polymethoxylated 3-(bromomethyl)flavones, and evaluated their antiproliferative activity against HL60. Results: 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. Conclusion: 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.