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

Abstract

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).

The Antioxidant Activity of Prenylflavonoids

“…Several derivatives were also isolated from Moraceae [16,20,[37][38][39], Asteraceae [24] and Cannabaceae [12][13][14] families. A great number of prenylated flavanones were collected from propolis of different origins [47,48] and some of them were obtained by synthesis [12,14,49] (compounds 77-118, Table 4).…”

Hop By-Products: Pharmacological Activities and Potential Application as Cosmetics

“…According to Bocquet et al, it was possible to demonstrate that desmethylxanthohumol in H. lupulus has antifungal activity against Zymoseptoria tritici (MIC value of 0.63 g/L) [42]. Additionally, it was found that xanthohumol can inhibit the growth of three Fusarium species, with MIC values from 0.015 to 0.100 mg/mL [43]. Additionally, Yin-Fang Yan showed in his work that ethanolic extracts of H. lupulus showed moderate antifungal activity against pathogenic fungi, while isoxanthohumol, an isoprene flavonoid from H. lupulus, showed high antifungal activity, in particular against B. cinerea.…”

Prevention of Fine Dust-Induced Vascular Senescence by Humulus lupulus Extract and Its Major Bioactive Compounds

“…Hops are a major source of phenolic compounds, and numerous animal and clinical experiments have asserted that the antioxidant properties of hops are related to the beneficial effects of their polyphenols [22]. Among the hop prenylflavonoids, XN and IX have been shown to have significant antioxidant potential [55][56][57][58]. The direct radical scavenging ability of XN and IX varies depending on the experimental methods.…”