RESUMEN
Interactions of two newly synthesized and six previously reported benzoxanthene lignans (BXLs), analogues of rare natural products, with DNA/RNA, G-quadruplex and HSA were evaluated by a set of spectrophotometric methods. Presence/absence of methoxy and hydroxy groups on the benzoxanthene core and minor modifications at C-1/C-2 side pendants - presence/absence of phenyl ring and presence/absence of methoxy and hydroxy groups on phenyl ring - influenced the fluorescence changes and the binding strength to double-stranded (ds-) and G-quadruplex structures. In general, compounds without phenyl ring showed stronger fluorescence changes upon binding than phenyl-substituted BXLs. On the other hand, BXLs with an unsubstituted phenyl ring showed the best stabilization effects of G-quadruplex. Circular dichroism spectroscopy results suggest mixed binding mode, groove binding and partial intercalation, to ds-DNA/RNA and end-stacking to top or bottom G-tetrads as the main binding modes of BXLs to those targets. All compounds exhibited micromolar binding affinities toward HSA and an increased protein thermal stability. Moderate to strong antiradical scavenging activity was observed for all BXLs with hydroxy groups at C-6, C-9 and C-10 positions of the benzoxanthene core, except for derivative bearing methoxy groups at these positions. BXLs with unsubstituted or low-substituted phenyl ring and one derivative without phenyl ring showed strong growth inhibition of Gram-positive Staphylococcus aureus. All compounds showed moderate to strong tumor cell growth-inhibitory activity and cytotoxicity.
Asunto(s)
Antineoplásicos/farmacología , ADN Tumoral Circulante/química , Lignanos/farmacología , ARN Neoplásico/química , Albúmina Sérica Humana/química , Xantenos/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Escherichia coli K12/citología , Escherichia coli K12/efectos de los fármacos , Humanos , Lignanos/síntesis química , Lignanos/química , Estructura Molecular , Salmonella enterica/citología , Salmonella enterica/efectos de los fármacos , Staphylococcus aureus/citología , Staphylococcus aureus/efectos de los fármacos , Relación Estructura-Actividad , Células Tumorales Cultivadas , Xantenos/síntesis química , Xantenos/químicaRESUMEN
Waste landfills represent a global problem, which is more pronounced in developing countries because of the lack of resources to implement procedures that include separation and waste processing. The aim of this research was to analyze leachate and ground waters samples at the site, upstream and downstream from the landfill during different year seasons on a registered non-hazardous waste dump and to conduct physico-chemical and biological assays to determine potential risk for the ecosystem. Potential cytotoxic, prooxidative and mutagenic effects of leachates and water samples were evaluated on human laryngeal cell line (HEp2). Leachates collected at landfill site caused genotoxic effect and had a higher pH, chemical oxygen demand (COD), biochemical oxygen demand (BOD) and elevated concentrations of phosphorus, chloride, nitrogen compounds and sulphate. Genotoxicity of the leachate was increased in samples collected in dry and warm period of the year. These results are in accordance to the physico-chemical analysis which revealed that during summer period, because of intense degradation process at high temperatures increased concentrations of different chemicals can be found in leachate. Groundwater collected downstream and upstream from landfill did not show statistically significant (geno)toxic effect, irrespective of the sampling season. Chemical analysis revealed that all compounds in groundwater were below permitted values. Purification process at landfill is effective and compounds that reach groundwater do not represent a toxicological threat.
Asunto(s)
Agua Subterránea/química , Mutágenos/análisis , Eliminación de Residuos/métodos , Instalaciones de Eliminación de Residuos , Contaminantes Químicos del Agua/análisis , Análisis de la Demanda Biológica de Oxígeno , EcosistemaRESUMEN
Native Crocus taxa are abundant in regions with moderate and dry climate; however, their potential in the food industry has thus far been neglected. The objective of this study was to compare the quantitative and qualitative flavonoid content and antioxidant and cytotoxic activity in organs of several populations of Croatian native taxa and assess their potential for application in the food industry. The dominant flavonoids in the native Crocus taxa were kaempferol and quercetin. Tepals contained similar or higher concentrations of flavonoid-glycosides than other organs. Tepals from Cvv1 and Cvv2 populations contained more flavonoid-glycosides than the commonly used spice saffron (C. sativus stigmas). The FRAP antioxidant activity of Cvv1 and Cvv5 tepals was similar to that of standard Trolox. DPPH inhibition of Cvv1 and Cvv3 tepals was within the range of that recorded for saffron. Cvv1 tepals significantly reduced reactive oxygen species in the broadest concentration range (50-1000 µg/ml), and showed considerable antioxidant activity in the ABTS assay, equal to 82% of standard Trolox antioxidant activity. A significantly higher concentration of kaempferol-rutinoside was recorded in this than in other taxa. The flavonoid showed a very strong or strong correlation with antioxidant assays results, and a negative correlation with cellular reactive oxygen species concentration. We therefore presumed that kaempferol-rutinoside is one of the main antioxidant phenolics in Crocus tepals. None of the tested extracts showed cytotoxicity toward Caco-2 cells. The results revealed that Cvv tepals have potential as a food supplement and are a promising material for further food safety tests.
Asunto(s)
Antioxidantes/análisis , Crocus/química , Suplementos Dietéticos/análisis , Flavonoides/análisis , Extractos Vegetales/farmacología , Antioxidantes/farmacología , Células CACO-2 , Flavonoides/farmacología , Humanos , Quempferoles/análisis , Fenoles/análisis , Extractos Vegetales/química , Quercetina/análisis , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Obesity is composed of multifunctional interactions of eating habits, behaviors, microbiota, genetics, and other unknown factors. We hypothesize that correlations occur between the fat mass and obesity-associated single nucleotide polymorphisms (FTO SNPs), the composition of microorganisms in the saliva, and life habits in obese women from Zagreb County. Our results of the analysis of 3 FTO SNPs showed a statistically significant positive correlation among the frequencies of the high-risk genotypes AA rs9939609 (P = .0367), CC rs1421085 (P = .0367), and GG rs17817449 (P = .0065) of the FTO gene in obese cases. Interestingly, 39.13% of obese women were triple homozygous for all 3 risk alleles. Furthermore, the composition of the oral microbiota in the obese group showed a higher occurrence of a major human pathogen, bacterium Staphylococcus aureus, but a significantly low presence of bacteria Streptococcus oralis, Streptococcus mitis, and Serratia ureilytica compared with the control group. The investigation also revealed that obese women prefer to consume candy and snacks and more meat and meat-derived products, sleep less than 6 hours per day, and had higher hypertension in comparison with the control group. These results support the hypothesis that female obesity is strongly related to all 3 variants of the FTO gene and perhaps a specific composition of microbiota in saliva due to dietary habits. Considering the bimodal distribution of the SNPs and bacterial content of saliva in obese women taken together are factors to consider for risk of obesity.