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2017 | 64 | 3 | 577-583
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Synthesis and biological evaluation of 4'-O-acetyl-isoxanthohumol and its analogues as antioxidant and antiproliferative agents

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Isoxanthohumol (2) and its 4'-O-monoacylated (3) and 7,4'-O-diacetylated (4) derivatives were synthesized and evaluated in vitro for their cytotoxic activity against several cancer cell lines of various origins: MCF-7 (breast), A549 (lung), MESSA (uterine sarcoma), LoVo (colon), drug-resistant human cancer cells (MESSA/DX and LoVo/DX), glioblastoma (U-118 MG), and also towards the non-cancerous cell line MCF-10A (normal breast cells). An antiproliferative assay indicates that 7,4'-di-O-acylisoxanthohumol (4) has similar cytotoxicity to its precursor, isoxanthohumol (2), against selected cell lines (A549, MES-SA, MES-SA/5DX, and U-118 MG). Compound 4 was only slightly more cytotoxic to lung, colon, breast (cancerous and normal) and uterine sarcoma (drug sensitive and drug resistant) cell lines compared to its monoacylated derivative (3). Both acylated isoxanthohumols showed preferential activity against tumor cells (MCF-7) and low cytotoxicity to normal cells (MCF-10A), which suggests selectivity of the acylated isoxanthohumols towards cancer cells. Additionally, the activity of the acylated isoxanthohumols was higher than for 2. To the best of our knowledge this is the first report on bioactivity of monoacylated isoxanthohumol (3) and its ester derivatives as antiproliferative compounds in drug resistant cell cultures. Acylation of 2 decreased the antioxidant activity determined by the DPPH method in the order isoxanthohumol (2) >4'-O-acetylisoxanthohumol (3) >7,4'-di-O-acetylisoxanthohumol (4).
Physical description
  • Faculty of Medicine, Centre for Innovative Research in Medical and Natural Sciences, University of Rzeszów, Rzeszów, Poland
  • Department of Biochemistry, Faculty of Medicine, University of Rzeszów, Rzeszów, Poland
  • Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Department of Experimental Oncology, Wrocław, Poland
  • Faculty of Medicine, Centre for Innovative Research in Medical and Natural Sciences, University of Rzeszów, Rzeszów, Poland
  • Department of Biochemistry, Faculty of Medicine, University of Rzeszów, Rzeszów, Poland
  • Faculty of Chemistry, Rzeszów University of Technology, Rzeszów, Poland
  • Department of Human Immunology, Faculty of Medicine, University of Rzeszów, Rzeszów Poland
  • Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Department of Experimental Oncology, Wrocław, Poland
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