Antioxidant, Cytotoxic, Genotoxic, and DNA-Protective Potential of 2,3-Substituted Quinazolinones: Structure—Activity Relationship Study

The evaluation of antioxidant compounds that counteract the mutagenic effects caused by the direct action of reactive oxygen species on DNA molecule is of considerable interest. Therefore, a series of 2,3-substituted quinazolinone derivatives (Q1–Q8) were investigated by different assays, and the relationship between their biological properties and chemical structure was examined. Genotoxicity and the potential DNA-protective effects of Q1–Q8 were evaluated by comet assay and DNA topology assay. Antioxidant activity was examined by DPPH-radical-scavenging, reducing-power, and total antioxidant status (TAS) assays. The cytotoxic effect of compounds was assessed in human renal epithelial cells (TH-1) and renal carcinoma cells (Caki-1) by MTT assay. Analysis of the structure–activity relationship disclosed significant differences in the activity depending on the substitution pattern. Derivatives Q5–Q8, bearing electron-donating moieties, were the most potent members of this series. Compounds were not genotoxic and considerably decreased the levels of DNA lesions induced by oxidants (H2O2, Fe2+ ions). Furthermore, compounds exhibited higher cytotoxicity in Caki-1 compared to that in TH-1 cells. Substantial antioxidant effect and DNA-protectivity along with the absence of genotoxicity suggested that the studied quinazolinones might represent potential model structures for the development of pharmacologically active agents

New Unnatural Gallotannins: A Way toward Green Antioxidants, Antimicrobials and Antibiofilm Agents

Nature has been a source of inspiration for the development of new pharmaceutically active agents. A series of new unnatural gallotannins (GTs), derived from d-lyxose, d-ribose, l-rhamnose, d-mannose, and d-fructose have been designed and synthesized in order to study the protective and antimicrobial effects of synthetic polyphenols that are structurally related to plant-derived products. The structures of the new compounds were confirmed by various spectroscopic methods. Apart from spectral analysis, the antioxidant activity was evaluated by 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging and iron reducing power (FRAP) assays. Antibacterial activity of compounds was tested in vitro against Staphylococcus aureus ATCC 29213, Enterococcus faecalis ATCC 29212 (reference and control strains), three methicillin-resistant isolates of S. aureus, and three isolates of vancomycin-resistant E. faecalis. For screening of antimycobacterial effect, a virulent isolate of Mycobacterium tuberculosis and two non-tuberculous mycobacteria were used. Furthermore, antibiofilm activity of structurally different GTs against S. aureus, and their ability to inhibit sortase A, were inspected. Experimental data revealed that the studied GTs are excellent antioxidants and radical-scavenging agents. The compounds exhibited only a moderate antibacterial effect against Gram-positive pathogens S. aureus and E. faecalis and were practically inactive against mycobacteria. However, they were efficient inhibitors and disruptors of S. aureus biofilms in sub-MIC concentrations, and interacted with the quorum-sensing system in Chromobacteriumviolaceum. Overall, these findings suggest that synthetic GTs could be considered as promising candidates for pharmacological, biomedical, consumer products, and for food industry applications

Quercetin decreases fructose drinking in model of fructose-induced insulin resistance. Antioxidant effects of fructose - methyl cellulose combination

The excessive fructose consumption is linked with metabolic changes and serious health problems. Overconsumption of fructose-sweetened food products mainly sugar-sweetened beverages is associated with body-weight gain, obesity, inflammation and cardiometabolic disturbances. The majority of fructose is metabolized in liver and an excess of fructose is converted to fat. The triglycerides are taken up by the adipose tissue for storage– consequently the fructose fed rats display enhancement of the adipose tissue mass and elevated blood uric acid. High fructose intake increases oxidation stress. Quercetin is one of the most commonly occurring bioactive flavonoids in human foods. It is present in tea, apples, broccoli, onion berries and red grapes. The quercetin is known for its beneficial health effects including mainly anti-inflammatory and antioxidant properties. In the presented study we adopted rats with fully developed fructose induced insulin resistance (9 weeks of 10% fructose treatment) which were then continuously treated with combination of fructose and 20 mg/kg/day quercetin for additional 6 weeks. Quercetin was delivered by gavage as solubilized in 1% methyl cellulose. Our results showed that quercetin treatment lead to the normalization of the fructose solution drinking to the level of drinking water intake as well as the decrease of plasma glucose in rats consuming fructose. Moreover, a significant decrease of plasma uric acid, oxidative stress biomarkers (TBARS, nitrotyrosine), AGEs fluorescence and hemoglobin leakage was induced by combination of fructose with methyl cellulose. Thus, methyl cellulose with fructose had positive impacts like antioxidant, anti-glycation and erythrocyteprotective effects. We might speculate that methyl cellulose possibly shifts the fructose metabolism in favour of utilization of antioxidant features of fructose. Moreover, in vitro experiments showed that fructose and methyl cellulose had a moderate antioxidant activity with additive effect showed in the ferric reducing antioxidant power assay.Redox Biology Congress 2023 : Abstracts : 6-9 June 2023, Vienna, Austri

Quercetin decreases fructose drinking in model of fructose-induced insulin resistance. Unexpected uric acid and TBARS lowering effect of methyl cellulose vehicle and fructose combination

The aim of this study was to improve insulin sensitivity in fructose-treated animals by ingestion of flavonoid quercetin. Several signs of insulin resistance have been developed in rats by drinking 10% fructose solution for 9 weeks. The effect of 6-week-gavage-administrated quercetin (20 mg/kg/day in 1% methyl cellulose solution) was monitored. Rats of the control groups received methyl cellulose vehicle as well. The most striking result of the quercetin treatment was the normalization of the fructose solution drinking to the level of drinking water intake. In addition, quercetin supplementation considerably decreased the plasma glucose and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) index in rats consuming fructose. Surprisingly, fructose ingestion did not elevate plasma uric acid, thiobarbituric acid reactive substances, nitrotyrosine, or advanced glycation end products fluorescence. Instead, a reduction of the above parameters was observed. In summary, these results indicate that quercetin supplementation reduces fructose drinking and decreases plasma glucose and the HOMA-IR index. Furthermore, methyl cellulose, in combination with fructose, causes uric acid – lowering, antioxidant and anti-glycation effects. Thus, methyl cellulose possibly shifts fructose metabolism in favor of the utilization of antioxidant features of fructose. Our results call for using methyl cellulose in sweetened beverages and other sweetened food