Anti-Cancer Activity and Mutagenic Potential of Novel Copper (II) Quinolinone Schiff Base Complexes in Hepatocarinoma Cells

This study determined the cytotoxic, cyto-selective and mutagenic potential of novel quinolinone Schiff base ligands and their corresponding copper(II) complexes in human-derived hepatic carcinoma cells (Hep-G2) and non-malignant human-derived hepatic cells (Chang). Results indicated that complexation of quinolinone Schiff bases with copper served to significantly enhance cytotoxicity. Here, the complex of (7E)-7-(3-ethoxy-2-hydroxybenzylideamino)-4-methylquinolin-2(1H)-one (TV117-FM) exhibited the lowest IC50 value (17.9 μM) following 96 h continuous exposure, which was comparable to cisplatin (15.0 μM). However, results revealed that TV117-FM lacked cytoselectivity over non-malignant cells. Additionally, the complex was minimally effluxed from cells via Pglycoprotein (P-gp) and was shown to be non-mutagenic in the Standard Ames test. Furthermore, BrdU incorporation assays showed that it was capable of inhibiting DNA synthesis in a concentrationand time-dependent manner. However, inhibition was not as a consequence of DNA intercalation, as illustrated in electrophoretic mobility shift assays. Interestingly, it was shown that the ligand was capable of inhibiting the action of topoisomerase II, but this was lost following complexation. This indicated that the mechanism of action of the novel copper(II) complex was different from that of the parent ligand and suggests that TV117-FM may have a therapeutic role to play in the treatment of hepatocellular carcinoma. Studies are currently underway to elucidate the exact in vitro mechanism of action of this novel, metal-based anti-cancer agent

Synthesis, characterization and antimicrobial activity of a series of substituted coumarin-3-carboxylatosilver(1) complexes

A series of new coumarin-derived carboxylate ligands and their silver(I) complexes have been synthesized, characterized and screened for their in vitro antibacterial activity against a range of Gram-positive and Gram-negative bacteria as well as for their antifungal activity against a clinical isolate of Candida albicans. The ligands were synthesised by either acid or base hydrolysis of their corresponding esters, which in turn were synthesised via the Knoevenegal reaction. The reaction of silver(I) nitrate with the coumarin carboxylate ligands in either aqueous or aqueous/ethanol solutions allowed the isolation of a series of novel Ag(I) carboxylate complexes. Whilst none of the ligands showed any antimicrobial activity, a number of the Ag(I) complexes exhibited potent activity. In particular, Ag(I) complexes of hydroxy-substituted coumarin carboxylates demonstrated potent activity against the clinically important methicillin-resistant Staphylococcus aureus (MRSA) bacterium (MIC80 = 0.63 μM)

When is an image a health claim? A false-recollection method to detect implicit inferences about products' health benefits

Objective: Images on food and dietary supplement packaging might lead people to infer (appropriately or inappropriately) certain health benefits of those products. Research on this issue largely involves direct questions, which could (a) elicit inferences that would not be made unprompted, and (b) fail to capture inferences made implicitly. Using a novel memory-based method, in the present research, we explored whether packaging imagery elicits health inferences without prompting, and the extent to which these inferences are made implicitly. Method: In 3 experiments, participants saw fictional product packages accompanied by written claims. Some packages contained an image that implied a health-related function (e.g., a brain), and some contained no image. Participants studied these packages and claims, and subsequently their memory for seen and unseen claims were tested. Results: When a health image was featured on a package, participants often subsequently recognized health claims that—despite being implied by the image—were not truly presented. In Experiment 2, these recognition errors persisted despite an explicit warning against treating the images as informative. In Experiment 3, these findings were replicated in a large consumer sample from 5 European countries, and with a cued-recall test. Conclusion: These findings confirm that images can act as health claims, by leading people to infer health benefits without prompting. These inferences appear often to be implicit, and could therefore be highly pervasive. The data underscore the importance of regulating imagery on product packaging; memory-based methods represent innovative ways to measure how leading (or misleading) specific images can be. (PsycINFO Database Record (c) 2016 APA, all rights reserved

Mechanism of action of coumarin and silver(I)- coumarin complexes against the pathogenic yeast Candida albicans

The anti-fungal activity and mode of action of a range of silver(I)- coumarin complexes was examined. The most potent silver(I)- coumarin complexes, namely 7-hydroxycoumarin-3-carboxylatosilver(I), 6-hydroxycoumarin-3-carboxylatosilver(I) and 4-oxy-3-nitrocoumarinbis(1,10-phenanthroline)silver(I), had MIC80 values of between 69.1 and 4.6 M against the pathogenic yeast Candida albicans. These compounds also reduced respiration, lowered the ergosterol content of cells and increased the trans-membrane leakage of amino acids. A number of the complexes disrupted cytochrome synthesis in the cell and induced the appearance of morphological features consistent with cell death by apoptosis. These compounds appear to act by disrupting the synthesis of cytochromes which directly aVects the cell's ability to respire. A reduction in respiration leads to a depletion in ergosterol biosynthesis and a consequent disruption of the integrity of the cell membrane. Disruption of cytochrome biosynthesis may induce the onset of apoptosis which has been shown previously to be triggered by alteration in the location of cytochrome c. Silver(I)- coumarin complexes demonstrate good anti-fungal activity and manifest a mode of action distinct to that of the conventional azole and polyene drugs thus raising the possibility of their use when resistance to conventional drug has emerged or in combination with such drugs

Anticancer and Antifungal Activity of Copper(II) Complexes of Quinolin-2(1H)-one-Derived Schiff Bases

The condensation of substituted aromatic aldehydes with 7-amino-4-methyl-quinolin-2(1H)-one (1) has lead to the isolation of quinolin-2(1H)-one derived Schiff bases (2–14). The copper(II) complexes (2a–14a) of the ligands were also prepared, and together with their corresponding free ligands were fully characterised by elemental analyses, spectral methods (IR, 1H and 13C NMR, AAS, UV–Vis), magnetic and conductance measurements. The bidentate ligands coordinated to the copper(II) ion through the deprotonated phenolic oxygen and the azomethine nitrogen of the ligands in almost all cases. X-ray crystal structures of two of the complexes, 5a and 8a, confirmed the bidentate coordination mode. All of the compounds were investigated for their antimicrobial activities against the fungus, Candida albicans, and against Gram-positive and Gram-negative bacteria. The compounds were found to have excellent anti-Candida activity but were inactive against Staphylococcus aureus and Escherichia coli. Selected compounds (2–8 and 2a–8a) were also screened for their in vitro anticancer potential using the human hepatic carcinoma cell line, Hep-G2. Several derivatives were shown to be active comparable to that of cisplatin

Anticancer and antifungal activity of copper(II) complexes of quinolin-2(1H)-one-derived Schiff bases

The condensation of substituted aromatic aldehydes with 7-amino-4-methyl-quinolin-2(1H)-one (1) has lead to the isolation of quinolin-2(1H)-one derived Schiff bases (2–14). The copper(II) complexes (2a–14a) of the ligands were also prepared, and together with their corresponding free ligands were fully characterised by elemental analyses, spectral methods (IR, 1H and 13C NMR, AAS, UV–Vis), magnetic and conductance measurements. The bidentate ligands coordinated to the copper(II) ion through the deprotonated phenolic oxygen and the azomethine nitrogen of the ligands in almost all cases. X-ray crystal structures of two of the complexes, 5a and 8a, confirmed the bidentate coordination mode. All of the compounds were investigated for their antimicrobial activities against the fungus, Candida albicans, and against Gram-positive and Gram-negative bacteria. The compounds were found to have excellent anti-Candida activity but were inactive against Staphylococcus aureus and Escherichia coli. Selected compounds (2–8 and 2a–8a) were also screened for their in vitro anticancer potential using the human hepatic carcinoma cell line, Hep-G2. Several derivatives were shown to be active comparable to that of cisplatin

Role of cell cycle events and apoptosis in mediating the anti-cancer activity of a silver(I) complex of 4-hydroxy-3-nitro-coumarin-bis(phenanthroline) in human malignant cancer cells.

The central objective of the current study was to investigate the potential in vitro anti-proliferative effect of 4-hydroxy-3-nitro-coumarin (hncH), and the mixed-ligand silver (I) complex of 4-oxy-3-nitro-coumarin-bis (phenanthroline), [Ag(hnc)(phen)2] using four human-derived model cell lines. In addition, selected mechanistic studies were carried out using the most sensitive of the four cell lines. Results obtained show that the complex could decrease the proliferation of all four cell lines including neoplastic renal and hepatic, namely A-498 and HepG2 cells, respectively, along with two non-neoplastic renal and hepatic cell lines, HK-2 and Chang, respectively. Furthermore, non-neoplastic hepatic cells (Chang) appeared to be less sensitive to the effect of the complex, but this effect was not replicated in the non-neoplastic renal (HK-2) cells. Based on IC50 values [Ag(hnc)(phen)2] was shown to be almost four times more potent than cisplatin, using HepG2 cells. In addition, the observed anti-proliferative effect was shown to be both dose- and time-dependent. Furthermore, the complex was shown to decrease DNA synthesis, but did not intercalate with it. Moreover, there was no evidence that P-glycoprotein-mediated multi-drug resistance was likely to decrease antiproliferative activity. Cytological stains, analysis of genomic DNA, and biochemical assays [caspase-3 and -9 and cleaved poly(ADP-ribose)-polymerase protein] showed that cell death appeared to result from apoptosis, with the possibility of secondary necrosis. Additionally, flow cytometric analysis showed that the complex functioned through an alteration in cell cycle progression. Taken together, [Ag(hnc)(phen)2] has been shown to be a more potent anti-proliferative agent than cisplatin, capable of altering key biochemical events leading to cell death. Additional mechanistic studies are underway to probe more fully its mechanism of action

The Impact of Nutrition and Health Claims on Consumer Perceptions and Portion Size Selection: Results from a Nationally Representative Survey

Nutrition and health claims on foods can help consumers make healthier food choices. However, claims may have a ‘halo’ effect, influencing consumer perceptions of foods and increasing consumption. Evidence for these effects are typically demonstrated in experiments with small samples, limiting generalisability. The current study aimed to overcome this limitation through the use of a nationally representative survey. In a cross-sectional survey of 1039 adults across the island of Ireland, respondents were presented with three different claims (nutrition claim = “Low in fat”; health claim = “With plant sterols. Proven to lower cholesterol”; satiety claim = “Fuller for longer”) on four different foods (cereal, soup, lasagne, and yoghurt). Participants answered questions on perceived healthiness, tastiness, and fillingness of the products with different claims and also selected a portion size they would consume. Claims influenced fillingness perceptions of some of the foods. However, there was little influence of claims on tastiness or healthiness perceptions or the portion size selected. Psychological factors such as consumers’ familiarity with foods carrying claims and belief in the claims were the most consistent predictors of perceptions and portion size selection. Future research should identify additional consumer factors that may moderate the relationships between claims, perceptions, and consumption

Prevalence of Nutrition and Health-Related Claims on Pre-Packaged Foods: A Five-Country Study in Europe

This study is part of the research undertaken in the EU funded project CLYMBOL (“Role of health-related CLaims and sYMBOLs in consumer behaviour”). The first phase of this project consisted of mapping the prevalence of symbolic and non-symbolic nutrition and health-related claims (NHC) on foods and non-alcoholic beverages in five European countries. Pre-packaged foods and drinks were sampled based on a standardized sampling protocol, using store lists or a store floor plan. Data collection took place across five countries, in three types of stores. A total of 2034 foods and drinks were sampled and packaging information was analyzed. At least one claim was identified for 26% (95% CI (24.0%–27.9%)) of all foods and drinks sampled. Six percent of these claims were symbolic. The majority of the claims were nutrition claims (64%), followed by health claims (29%) and health-related ingredient claims (6%). The most common health claims were nutrient and other function claims (47% of all claims), followed by disease risk reduction claims (5%). Eight percent of the health claims were children’s development and health claims but these were only observed on less than 1% (0.4%–1.1%) of the foods. The category of foods for specific dietary use had the highest proportion of NHC (70% of foods carried a claim). The prevalence of symbolic and non-symbolic NHC varies across European countries and between different food categories. This study provides baseline data for policy makers and the food industry to monitor and evaluate the use of claims on food packaging

The effect of diet on the physical and mental development of children: views of parents and teachers in four European countries

Although the impact of diet on physical health is an important public health issue, less attention has been devoted to the relationship between nutrition and children's mental development. The views of parents and teachers about the extent to which diet affects physical and mental development of children were compared in four European countries. An online questionnaire (developed in English and translated) was circulated through a market research agency. Participants were parents or teachers of children aged 4-10 years without learning or behavioural issues. Questionnaires were returned by 1606 parents (401 in England, Germany and Hungary; 403 in Spain) and 403 teachers (100 in each country, except for 103 in Hungary). Teachers were older than parents (35·3 % v. 18·3 % over 45 years; P<0·001) and less likely to smoke (15·9 % v. 26·3 %, P<0·001). There was no difference between the proportions of parents and teachers who felt that a child's physical development depended very much/extremely (v. moderately/slightly/not at all) on diet (overall 79·8 %). Lower proportions of both groups thought that mental development was very much/extremely influenced by diet (67·4 %). In the regression modelling, believing that physical and mental performance was greatly influenced by diet was significantly and positively associated with living in Hungary, scoring higher on a measure of General Health Interest and (parents only) level of education attained. Differences existed among countries in most views. Lower levels of awareness of the importance of diet for brain development and cognition (compared with physical health outcomes) indicate the potential for educating consumers, especially parents with lower educational attainment