Synthesis and biological evaluation of acyl derivatives of hydroxyflavones as potent antiproliferative agents against drug resistance cell lines

The synthesis of hydroxyflavone derivatives is described. The acyl derivatives of 3-, 6-, 7-hydroxyflavones (compounds 2, 4, 6, respectively) and chrysin (5,7-dihydroxyflavone, 7) were obtained in high yields and evaluated in vitro for their cytotoxic activity against several Cancer cell lines of different origin: MCF-7 (breast Cancer), A549 (nonsmall cell lung Cancer), MES-SA (uterine sarcoma), LoVo (colon Cancer), drug-resistant human Cancer cells (MES-SA/DX5, LoVo/DX) and also towards non-cancer cell line MCF-10A (normal breast epithelial cells). The Flavones modified with acyl group showed higher antiproliferative activity than free hydroxyflavones. The highest activity was noted for 3-acetoxyflavone (2), which proved active against LoVo, LoVo/DX, and MES-SA cell lines (IC50 from 4.7 μM to 7.8 μM, respectively). The highest ability to overcome the barrier of resistance (resistance index=0.82) against the drug-resistant MES-SA/DX5 cells compared to the parental drug-sensitive MES-SA cell line was found for 7-acetoxyflavone (6).

O-acylated flavones; antiproliferative effect; hydroxyflavones.