Accessible Unlicensed Requires Authentication Published by De Gruyter November 8, 2017

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

Monika Stompor, Marta Świtalska and Joanna Wietrzyk

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).

Acknowledgments

This work was supported by funding from the National Science Centre, Poland (2017/01/X/NZ9/00161). We would like to thank Dr. Bogdan Myśliwiec from the Faculty of Chemistry, Laboratory of Spectrometry, Rzeszow University of Technology, for NMR measurements.

  1. Conflict of interest statement: The authors declare that they have no conflict of interest.

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Received: 2017-5-22
Revised: 2017-10-14
Accepted: 2017-10-16
Published Online: 2017-11-8
Published in Print: 2018-1-26

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