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

  • Z Naturforsch C J Biosci. 2018 Jan 26;73(1-2):87-93. doi: 10.1515/znc-2017-0093.
Monika Stompor  1 ,  Marta Świtalska  2 ,  Joanna Wietrzyk  2
Affiliations
  • 1. Faculty of Medicine, Centre for Innovative Research in Medical and Natural Sciences, University of Rzeszów, Warzywna 1a 35-310, Rzeszów, Poland, Phone: +48 17 851 68 55.
  • 2. Department of Experimental Oncology, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Weigla 12 53-114, Wrocław, Poland.
PMID: 29116937 DOI: 10.1515/znc-2017-0093
Abstract

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).

Keywords
O-acylated flavones; antiproliferative effect; hydroxyflavones.
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