Anti-oxidant activity and mechanism of action of trans-resveratrol in different lipid systems

The anti-oxidative properties of trans -resveratrol were studied in the concentration range 0.02–0.20% (8.8 × 10⁻⁴–8.8 × 10⁻³  M ) during autoxidation of pure triacylglycerols of lard (TGL) and of pure triacylglycerols of sunflower oil (TGSO), as well as of commercial sunflower oil at 100 °C. In sunflower oil trans -resveratrol showed no anti-oxidative activity. In pure lipid systems trans -resveratrol considerably retarded the oxidation process, the effect being stronger in the less oxidizable substrate (TGL). The effectiveness (stabilization factor F ), strength (oxidation rate ratio, ORR) and activity ( A = F /ORR) of the different anti-oxidant concentrations were determined. The activity A was found to increase dose dependency as follows: A =3750–15425 for TGL, A =79–207 for TGSO. The participation of trans -resveratrol in the side reactions of inhibited oxidation was discussed.     

One Question,Multiple Answers: Biochemical and Biophysical Screening Methods Retrieve Deviating Fragment Hit Lists

Fragment‐based lead discovery is gaining momentum in drug development. Typically, a hierarchical cascade of several screening techniques is consulted to identify fragment hits which are then analyzed by crystallography. Because crystal structures with bound fragments are essential for the subsequent hit‐to‐lead‐to‐drug optimization, the screening process should distinguish reliably between binders and non‐binders. We therefore investigated whether different screening methods would reveal similar collections of putative binders. First we used a biochemical assay to identify fragments that bind to endothiapepsin, a surrogate for disease‐relevant aspartic proteases. In a comprehensive screening approach, we then evaluated our 361‐entry library by using a reporter‐displacement assay, saturation‐transfer difference NMR, native mass spectrometry, thermophoresis, and a thermal shift assay. While the combined results of these screening methods retrieve 10 of the 11 crystal structures originally predicted by the biochemical assay, the mutual overlap of individual hit lists is surprisingly low, highlighting that each technique operates on different biophysical principles and conditions.     

Antioxidant activity screening of extracts from Sideritis species (Labiatae) grown in Bulgaria

Plant samples from several species and populations of the genus Sideritis (Labiatae) grown in Bulgaria (S scardica, S syriaca and S montana) were extracted with different solvents. Their antioxidant activities were determined by the β‐carotene bleaching test (BCBT), 2,2′‐diphenyl‐1‐picrylhydrazyl (DPPH^?) radical scavenging method and static headspace gas chromatography (HS‐GC) and compared with the antioxidant activity of two reference compounds of different polarity, viz butylated hydroxytoluene (BHT) and rosmarinic acid. The pure reference compounds were applied in a ten‐times lower concentration than the plant extracts. The highest antioxidant activity in the BCBT, close to that of BHT, was observed for the more apolar extracts. The inhibitory effect on β‐carotene bleaching of the polar extracts and rosmarinic acid was much lower than that of BHT. The inhibition of hexanal formation in bulk safflower oil by most of S syriaca and S scardica extracts was as effective as BHT but less so than rosmarinic acid. S montana extracts showed weak antioxidant or even pro‐oxidant properties. Extracts from butanol and from ethyl acetate and the total methanol extracts from all Sideritis plants studied showed a strong radical scavenging activity against DPPH^?, close to that of rosmarinic acid. S montana extracts were, as a whole, slightly weaker radical inhibitors than the extracts from the other two species. The antioxidant activity of Sideritis extracts was attributed to the presence of flavonoid and phenylpropanoid glycosides. Copyright © 2003 Society of Chemical Industry     

Natural antioxidants from herbs and spices

There is a growing interest in natural antioxidants found in plants because of the world‐wide trend toward the use of natural additives in food and cosmetics. Herbs and spices are one of the most important targets to search for natural antioxidants from the point of view of safety. This review presents the results on stabilization of lipids and lipid‐containing foods with different herbs and spices (ground materials or extracts) and reports the structure of the main antioxidatively acting compounds isolated from them. The review presents information about the antioxidative effects of rosemary, sage, oregano, thyme, ginger, summer savory, black pepper, red pepper, clove, marjoram, basil, peppermint, spearmint, common balm, fennel, parsley, cinnamon, cumin, nutmeg, garlic, coriander, etc. Among the herbs of the Labiatae family, rosemary has been more extensively studied and its extracts are the first marketed natural antioxidants. Sage and oregano, which belong to the same family, have gained the interest of many research groups as potential antioxidants.     

Kinetics of lipid oxidation in the presence of cinnamic acid derivatives

The effects of seven (prenyl‐ and methoxy‐) derivatives of cinnamic acid (0.1 mM) on the kinetics of lipid (sunflower oil triacylglycerols, TGSO) bulk phase oxidation at 80 °C have been compared. Synthesis of prenyl cinnamic acid derivatives: 3‐prenyl‐4‐hydroxy‐cinnamic acid (PHC), 3,5‐diprenyl‐4‐hydroxy‐cinnamic acid (DPHC), 2,2‐di‐methyl‐6‐carboxy‐ethenyl‐2H‐benzopyran (DMCB), 2,2‐dimethyl‐6‐carboxy‐ethenyl‐8‐prenyl‐2H‐benzopyran (DCEPB) present in Brazilian propolis has been performed. The monoprenyl derivative (PHC) has been found to exert a higher antioxidant activity as compared to the diprenyl derivative (DPHC). However, cinnamic acid derivatives DMCB and DCEPB have caused no change in the kinetics of TGSO oxidation. The results obtained have been compared with those on related compounds containing a cinnamic acid moiety as a structural feature, such as 4‐hydroxy‐cinnamic (p‐coumaric), 3‐methoxy‐4‐hydroxy‐cinnamic (ferulic) and 3,5‐dimethoxy‐4‐hydroxy‐cinnamic (sinapic) acids, as well as with data on butylated hydroxytoluene (BHT) and α‐tocopherol (αToc). PHC has shown a stronger antioxidant efficiency than BHT, p‐coumaric and ferulic acid, but a weaker antioxidant efficiency than α‐Toc and sinapic acid. The observed antioxidant effect of DPHC was stronger than that of p‐coumaric and ferulic acids and weaker than that of α‐Toc, BHT and sinapic acid.     

On the participation of fatty alcohols in the autoxidation of lipids

The influence of 1-tetradecanol, 1-hexadecanol, 1-octadecanol and 1-eicosanol in concentrations of 5 to 80 mmol kg^?1 on the autoxidation of various types of lipid systems (sunflower and olive oils, lard, tristearin and olive oil methyl esters) is investigated at 70–135°C. A pro-oxidative effect of the fatty alcohols introduced into the systems is established. The extent of this effect depends on the type and degree of unsaturation in the lipid system, its hydroperoxide content, and the chain length and concentration of the alcohols. A further factor is the valency of the alcohols with which the fatty acids are esterified; thus the pro-oxidative effect of the fatty alcohols is less pronounced with triacyl glycerols than with fatty acid methyl esters given the same oxidation rate. The results obtained are explained on the basis of the theory of a radical chain process of lipid oxidation.     

N‐3 fatty acids for human nutrition: stability considerations

Currently there is great interest in dietary n‐3 fatty acids to promote health. The food industry aims to produce food products enriched in α‐linolenic acid (Ln), eicosapentaenoic acid (EPA) and/or docosahexaenoic acid (DHA) to reduce some of the physiological effects of linoleic acid (L), the major polyunsaturated fatty acid in our diet. However, the goal is hampered by the susceptibility of the n‐3 fatty acids to oxidation. As a result the sensory and nutritional quality of such foods deteriorates. Lipid scientists therefore have to find a way to stabilise these fatty acids. Innovative technologies to protect n‐3 polyunsaturates using antioxidants, adequate preparation, refining and packaging of the oil are needed. In this paper we review the inherent stability and the stabilisation of these nutritionally valuable polyunsaturated fatty acids.     

Effect of lead ions on lipids and antioxidant complex activity of Capsicum annuum L leaves,pericarp and seeds

The composition of the main lipid classes in leaves, pericarp and seeds of pepper (Capsicum annuum L), and the effect of seedlings immersion in lead and sodium acetate nutrient solutions were investigated. Lead ions accumulated mainly in leaves; in pericarp and seeds the concentration of lead was more than 10 times lower. The influence of lead ions on the leaf lipid composition was expressed most in the last stages of plant development. Treatment with lead acetate caused a decrease in the activity of the antioxidative complex in pepper seeds.     

Effect of sitosterol on autoxidation rate and product composition in a model lipid system

The effect of 5% sitosterol on the autoxidation of tristearin at 120°C was investigated. It was found that sitosterol caused a two-fold increase in the process rate; this effect was unchanged at peroxide concentrations of up to 350 mEq kg^?-1. It was established that introduction of 5% sitosterol considerably increased the concentration of oxidised products in tristearin (from 0.5 to 6.5%) after oxidation at 120°C for 7h. The degree of oxidation of sitosterol in the system was found to be 56%. The structure and composition of oxidised products in the two lipid systems (tristearin, and tristearin+5% sitosterol) were determined. Conclusions were drawn concerning the effect of the lipid medium on the composition and structure of the products of sitosterol autoxidation.     

Structure-Based Optimization of Inhibitors of the Aspartic Protease Endothiapepsin

Aspartic proteases are a class of enzymes that play a causative role in numerous diseases such as malaria (plasmepsins), Alzheimer’s disease (β-secretase), fungal infections (secreted aspartic proteases), and hypertension (renin). We have chosen endothiapepsin as a model enzyme of this class of enzymes, for the design, preparation and biochemical evaluation of a new series of inhibitors of endothiapepsin. Here, we have optimized a hit, identified by de novo structure-based drug design (SBDD) and DCC, by using structure-based design approaches focusing on the optimization of an amide–π interaction. Biochemical results are in agreement with SBDD. These results will provide useful insights for future structure-based optimization of inhibitors for the real drug targets as well as insights into molecular recognition.