Study on the Synthesis and Structure-Activity Relationship of 3-Styrylflavones Possessing Nitrogenated D-ring Moiety

BACKGROUND/AIM: Flavones are naturally occurring compounds with a wide range of biological activities and therefore they represent a privileged scaffold in medicinal chemistry. We recently reported the systematic synthesis of 3-styrylflavones possessing variously hydroxylated D-ring moieties, which indicated significant antiproliferative activity. To determine how the bioisosteric replacement, such as the replacement of a hydroxyl group by an amino/nitro group, influences antiproliferative activity, we designed and synthesized a series of 3-styrylflavones possessing variously nitrogenated D-ring moieties. MATERIALS AND METHODS: 3-Styrylflavones with a nitrated D-ring were systematically synthesized by the Wittig reaction between several nitrated benzaldehydes and the 3-(bromomethyl)flavone derivatives prepared from 3-methylflavones, and 3-styrylflavones with an aminated D-ring were synthesized by the reduction of the corresponding 3-styrylflavones with a nitrated D-ring. Their antiproliferative activity against HL60 cells was evaluated. RESULTS: =44 μM). CONCLUSION: Introduction of a nitrogen atom to the D-ring moiety of 3-styrylflavones greatly increased the antiproliferative activity and the SAR study demonstrated the importance of 3-styrylflavones possessing a 2',3',4'-trimethoxyphenyl substituent as a new scaffold in anticancer drug design.