Synthesis and biological evaluation of new 4’-O-acetylisoxanthohumol and its analogues as antioxidant and antiproliferative agents
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 to 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 non-cancer cell line MCF-10A (normal breast cells). The antiproliferative assay indicated that 7,4’-di-O-acylisoxanthohumol (4) is similar cytotoxic to selected cell lines (A549, MES-SA, MES-SA/5DX, and U-118 MG) to those its precursor, isoxanthohumol (2). Compound 4 was only slightly more cytotoxic to lung, colon, breast (cancer 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 esters to cancer cells. Additionally, this activity was higher than for isoxanthohumol (2). To the best of our knowledge this is the first report on bioactivity of monoacylated isoxanthohumol (3) and its ester derivatives as apoptosis inducers toward drug resistant cell cultures. Acylation of IXN (2) led to decrease an antioxidant activity by the method of DPPH in the order isoxanthohumol (2) > 4’-O-acetylisoxanthohumol (3) > 7,4’-di-O-acetylisoxanthohumol (4), respectively.
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