Chemometric modelling to relate antioxidants, neutral lipid fatty acids and flavour components in chicken breast

Relationships among quality factors in retailed free-range, corn-fed, organic, and conventional chicken breasts (9) were modeled using chemometric approaches. Use of principal component analysis (PCA) to neutral lipid composition data explained the majority (93%) of variability (variance) in fatty acid contents in 2 significant multivariate factors. PCA explained 88 and 75% variance in 3 factors for, respectively, flame ionization detection (FID) and nitrogen phosphorus (NPD) components in chromatographic flavor data from cooked chicken after simultaneous distillation extraction. Relationships to tissue antioxidant contents were modeled. Partial least square regression (PLS2), interrelating total data matrices, provided no useful models. By using single antioxidants as Y variables in PLS (1), good models (r2 values > 0.9) were obtained for alpha-tocopherol, glutathione, catalase, glutathione peroxidase, and reductase and FID flavor components and among the variables total mono and polyunsaturated fatty acids and subsets of FID, and saturated fatty acid and NPD components. Alpha-tocopherol had a modest (r2 = 0.63) relationship with neutral lipid n-3 fatty acid content. Such factors thus relate to flavor development and quality in chicken breast meat.

Relationships between flavour, lipid composition and antioxidants in organic, free-range and conventional chicken breasts from modelling

Consumers expect organic, free-range and corn-fed chicken to be nutritionally wholesome and have premium flavour characters. Interrelationships between flavour, fatty acids and antioxidants of retailed breasts were explored using simple correlations and chemometrics. Saturated fatty acid C16:0, and n-6 polyunsaturated C20:4 and C22:4 contents were correlated with lipid oxidation products (thiobarbituric acid reactive substances) and in partial least-squares regression (PLS1) with 32 high-resonance gas chromatography (flame ionization) flavour components (r2>0.90), and also linked (r2>0.80) to antioxidants (-tocopherol, glutathione and catalase). A further 10 high-resonance gas chromatography nitrogen phosphorus detector flavour components were correlated (r 2>0.85) with C18:3(n-3) content. Chicken character was correlated with C18:3(n-3), and C18:3(n-6) inversely with oily, off-flavour and lipid oxidation. Sweet, fruity and oily aromas were linked in PLS1 with 13 specific fatty acids (r2>0.6), and bland taste with total summed (six) fatty acid fractions (r2>0.81). Specific antioxidants were correlated with sweet, fruity and chicken aromas, and -tocopherol inversely with lipid oxidation. PLS2 confirmed relationships between fatty acid composition, antioxidants and the subsets of 32 and 10 flavour components. Clear relationships were thus observed between lipid and antioxidant compositions and flavour in chicken breast meat.

Quinols as novel therapeutic agents. 2.1 4-(1-arylsulfonylindol- 2-yl)-4-hydroxycyclohexa-2,5-dien-1-ones and related agents as potent and selective antitumor agents

A series of substituted 4-(1-arylsulfonylindol-2-yl)-4-hydroxycyclohexa-2, 5-dien-1-ones (indolylquinols) has been synthesized on the basis of the discovery of lead compound 1a and screened for antitumor activity. Synthesis of this novel series was accomplished via the "one-pot" addition of lithiated (arylsulfonyl)indoles to 4,4-dimethoxycyclohexa-2,5-dienone followed by deprotection under acidic conditions. Similar methodology gave rise to the related naphtho-, 1H-indole-, and benzimidazole-substituted quinols. A number of compounds in this new series were found to possess in vitro human tumor cell line activity substantially more potent than the recently reported antitumor 4-substituted 4-hydroxycyclohexa-2,5-dien-1-ones1 with similar patterns of selectivity against colon, renal, and breast cell lines. The most potent compound in the series in vitro, 4-(1-benzenesulfonyl-6-fluoro-1H-indol- 2-yl)-4-hydroxycyclohexa-2,5-dienone (1h), exhibits a mean GI50 value of 16 nM and a mean LC50 value of 2.24 μM in the NCI 60-cell-line screen, with LC50 activity in the HCT 116 human colon cancer cell line below 10 nM. The crystal structure of the unsubstituted indolylquinol 1a exhibits two independent molecules, both participating in intermolecular hydrogen bonds from quinol OH to carbonyl O, but one OH group also interacts intramolecularly with a sulfonyl O atom. This interaction, which strengthens upon ab initio optimization, may influence the chemical environment of the bioactive quinol moiety. In vivo, significant antitumor activity was recorded (day 28) in mice bearing subcutaneously implanted MDA-MB-435 xenografts, following intraperitoneal treatment of mice with compound 1a at 50 mg/kg.

Silver carbonate nanoparticles stabilised over alumina nanoneedles exhibiting potent antibacterial properties

A simple method of preparing Ag2CO3 nanoparticles utilising high area γ-alumina nanoneedles has been developed; these are promising antimicrobial agents against diverse bacterial strains. © The Royal Society of Chemistry.

N-terminal His7-modification of glucagon-like peptide-1(7-36) amide generates dipeptidyl peptidase IV-stable analogues with potent antihyperglycaemic activity

Glucagon-like peptide-1(7-36)amide (GLP-1) possesses several unique and beneficial effects for the potential treatment of type 2 diabetes. However, the rapid inactivation of GLP-1 by dipeptidyl peptidase IV (DPP IV) results in a short half-life in vivo (less than 2 min) hindering therapeutic development. In the present study, a novel His7-modified analogue of GLP-1, N-pyroglutamyl-GLP-1 as well as N-acetyl-GLP-1 were synthesised and tested for DPP IV stability and biological activity. Incubation of GLP-1 with either DPP IV or human plasma resulted in rapid degradation of native GLP-1 to GLP-1(9-36)amide, while N-acetyl-GLP-1 and N-pyroglutamyl-GLP-1 were completely resistant to degradation. N-acetyl-GLP-1 and N-pyroglutamyl-GLP-1 bound to the GLP-1 receptor but had reduced affinities (IC50 values 32.9 and 6.7 nM, respectively) compared with native GLP-1 (IC50-37 nM). Similarly, both analogues stimulated cAMP production with EC50 values of 16.3 and 27 nM respectively compared with GLP-1 (EC50 4.7 nM). However, N-acetyl-GLP-1 and N-pyroglutamyl-GLP-1 exhibited potent insulinotropic activity in vitro at 5.6 mM glucose (P< 0.05 to P< 0.001) similar to native GLP-1. Both analogues (25 nM/kg body weight) lowered plasma glucose and increased plasma insulin levels when administered in conjunction with glucose (18 nM/kg body weight) to adult obese diabetic (ob/ob) mice. N-pyroglutamyl-GLP-1 was substantially better at lowering plasma glucose compared with the native peptide, while N-acetyl-GLP-1 was significantly more potent at stimulating insulin secretion. These studies indicate that N-terminal modification of GLP-1 results in DPP IV-resistant and biologically potent forms of GLP-1. The particularly powerful antihyperglycaemic action of N-pyroglutamyl-GLP-1 shows potential for the treatment of type 2 diabetes. © 2004 Society for Endocrinology.

Development of potent and selective tissue transglutaminase inhibitors:their effect on TG2 function and application in pathological conditions

Potent-selective peptidomimetic inhibitors of tissue transglutaminase (TG2) were developed through a combination of protein-ligand docking and molecular dynamic techniques. Derivatives of these inhibitors were made with the aim of specific TG2 targeting to the intra- and extracellular space. A cell-permeable fluorescently labeled derivative enabled detection of in situ cellular TG2 activity in human umbilical cord endothelial cells and TG2-transduced NIH3T3 cells, which could be enhanced by treatment of cells with ionomycin. Reaction of TG2 with this fluorescent inhibitor in NIH3T3 cells resulted in loss of binding of TG2 to cell surface syndecan-4 and inhibition of translocation of the enzyme into the extracellular matrix, with a parallel reduction in fibronectin deposition. In human umbilical cord endothelial cells, this same fluorescent inhibitor also demonstrated a reduction in fibronectin deposition, cell motility, and cord formation in Matrigel. Use of the same inhibitor in a mouse model of hypertensive nephrosclerosis showed over a 40% reduction in collagen deposition.

New genre of antioxidants from renewable natural resources:synthesis and characterisation of rosemary plant-derived antioxidants and their performance in polyolefins

Several ester derivatives of rosmarinic acid (rosmarinates) were synthesised, characterised (1D and 2D NMR, UV and FTIR spectroscopy) and tested for their potential use as antioxidants derived from a renewable natural resource. The intrinsic free radical scavenging activity of the rosmarinates was assessed, initially using a modified DPPH (2, 2-diphenyl-1-picrylhydrazyl radical) method, and found to be higher than that of commercial synthetic hindered phenol antioxidants Irganox 1076 and Irganox 1010. The thermal stabilising performance of the rosmarinates in polyethylene (PE) and polypropylene (PP) was subsequently examined and compared to that of samples prepared similarly but in the presence of Irganox 1076 (in PE) and Irganox 1010 (in PP) which are typically used for polyolefin stabilisation in industrial practice. The melt stability and the long-term thermo-oxidative stability (LTTS) of processed polymers containing the antioxidants were assessed by measuring the melt flow index (MFI), melt viscosity, oxidation induction time (OIT) and long-term (accelerated) thermal ageing performance. The results show that both the melt and the thermo-oxidative stabilisation afforded by the rosmarinates, and in particular the stearyl derivative, in both PE and PP, are superior to those of Irganox 1076 and Irganox 1010, hence their potential as effective sustainable bio-based antioxidants for polymers. The rosmarinic acid used for the synthesis of the rosmarinates esters in this study was obtained from commercial rosemary extracts (AquaROX80). Furthermore, a large number of different strains of UK-grown rosemary plants (Rosmarinum officinalis) were also extracted and analysed in order to examine their antioxidant content. It was found that the carnosic and the rosmarinic acids, and to a much lesser extent the carnosol, constituted the main antioxidant components of the UK-plants, with the two acids being present at a ratio of 3:1, respectively.

Grafting functional antioxidants on highly crosslinked polyethylene

The problem of interference of antioxidants, such as hindered phenols, with peroxide-initiated crosslinking of polyethylene was addressed through the use of functional (reactive) graftable antioxidants (g-AO). Reactive derivatives of hindered phenol and hindered amine antioxidants were synthesised, characterised and used to investigate their grafting reactions in high density polyethylene; both non-crosslinked (PE) and highly peroxide-crosslinked (PEXa). Assessment of the extent of in-situ grafting of the antioxidants, their retention after exhaustive solvent extraction in PE and PEXa, and the stabilising performance of the grafted antioxidants (g-AO) in the polymer were examined and benchmarked against conventionally stabilised crosslinked & non-crosslinked polyethylene. It was shown that the functional antioxidants graft to a high extent in PEXa, and that the level of interference of the g-AOs with the polymer crosslinking process was minimal compared to that of conventional antioxidants which bear the same antioxidant function. The much higher level of retention of the g-AOs in PEXa after exhaustive solvent extraction, compared to that of the corresponding conventional antioxidants, accounts for their superior long-term thermal stabilising performance under severe extractive conditions.