Synthesis and biological evaluation of 4'-O-acetyl-isoxanthohumol and its analogues as antioxidant and antiproliferative agents

• Authors: Monika Stompor , Marta Świtalska , Rafał Podgórski , Łukasz Uram , David Aebisher , Joanna Wietrzyk
• Languages of publication: EN

Abstracts

EN

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).

Keywords

EN

O-acylated flavanones; antiproliferative effect; isoxanthohumol; hop flavonoids

• Publisher: Polish Biochemical Society
• Journal: Acta Biochimica Polonica
• Year: 2017
• Volume: 64
• Issue: 3
• Pages: 577-583

Dates

published

2017

received

2017-05-10

revised

2017-07-01

accepted

2017-07-17

(unknown)

2017-08-12

Contributors

author

Monika Stompor

• 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

author

Marta Świtalska

• Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Department of Experimental Oncology, Wrocław, Poland

author

Rafał Podgórski

• 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

author

Łukasz Uram

• Faculty of Chemistry, Rzeszów University of Technology, Rzeszów, Poland

author

David Aebisher

• Department of Human Immunology, Faculty of Medicine, University of Rzeszów, Rzeszów Poland

author

Joanna Wietrzyk

• Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Department of Experimental Oncology, Wrocław, Poland

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Identifiers

DOI

10.18388/abp.2017_1608