Reference - Detail
| RRC ID | 89693 |
|---|---|
| Author | Tsutsumi A, Kawaii S, Yoshizawa Y. |
| Title | Study on the Synthesis and Structure-Activity Relationship of 3-Styrylflavones Possessing Nitrogenated D-ring Moiety. |
| Journal | Anticancer Res |
| Abstract |
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:27 3-Styrylflavones bearing nitrogenated D-ring moieties were successfully synthesized, and their antiproliferative activity was examined. The 3-(4‴-azastyryl)-2',3',4'-trimethoxyflavone (7Bf, IC50=32 μM) and 3-(3‴-azastyryl)-2',3',4'-trimethoxyflavone (7Be, IC50=34 μM) demonstrated the most effective activity, followed by 2‴-amino-3',4',5-trimethoxy-3-styrylflavone (6Bb, IC50=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. |
| Volume | 46(8) |
| Pages | 4183-4192 |
| Published | 2026-8-1 |
| DOI | 10.21873/anticanres.18279 |
| PII | 46/8/4183 |
| PMID | 42527095 |
| MeSH | Antineoplastic Agents* / chemical synthesis Antineoplastic Agents* / chemistry Antineoplastic Agents* / pharmacology Cell Proliferation / drug effects Flavones* / chemical synthesis Flavones* / chemistry Flavones* / pharmacology HL-60 Cells Humans Structure-Activity Relationship |
| Resource | |
| Human and Animal Cells | HL60(RCB0041) |