Structure-antioxidant Activity Relationship Research Articles

Flavanones in Citrus fruit: Structure–antioxidant activity relationships

Epidemiological surveys have shown an inverse relationship between the intake of fruit and the incidence of coronary heart disease and some type of cancer. Data found in the literature regarding the flavonoids in general while this study focuses on flavanones, a subclass of flavonoids which occurs in Citrus fruit. The aim of this work is to elucidate the antioxidant or pro-oxidant behaviours of some common flavanones and to determine their activity–structure relationships as antioxidant using the crocin bleaching inhibition assay. The compounds studied were regarding both the aglycon form and the glycoside form. Data evidence that the substitution of the 7th OH group of the flavanones by a neohesperidoside influences the relationship between structure and antioxidant activity. In fact, the 3′,4′-catechol structure and the O-methylation, in the aglycone forms, do not result significant. On the other hands, in the glycosylate forms, the 3′,4′-catechol structure noticeably increases the antioxidant power and the O-methylation decreases the antioxidant activity. The influence of the O-glycosylation with a rutinose molecule is neglectable.

Interactive effects of polyphenols, tocopherol and ascorbic acid on the Cu2+–mediated oxidative modification of human low density lipoproteins

Only limited knowledge is available about any interactions between phenolic compounds and other antioxidants in inhibiting LDL oxidation. Many foods and beverages contain high levels of phenolic compounds; therefore, these compounds should not be considered in isolation from each other. The aim of this study was to examine the structure-antioxidant activity relationship of quercetin, caffeic acid, epicatechin, hesperetin and phloretin as well as alpha-tocopherol and ascorbic acid through their ability to interact with copper ions. Isolated human LDL were incubated with single antioxidants or a combination of two and the kinetics of lipid peroxidation were assessed by measurement of conjugated diene formation (lag phase) via monitoring the absorbance at 234 nm after addition of copper ions. In addition, the degree of oxidation of the LDL protein moiety was followed by tryptophan fluorescence and carbonyl content measurements. Alpha-tocopherol and ascorbic acid showed a lower antioxidant activity in all test systems as compared to polyphenols at equimolar concentrations. Quercetin was the most effective compound in all three systems (p < 0.001 for lag phase and carbonyl content determination). A significant (p < 0.001) prolongation of the lag phase was found when combinations of ascorbic acid/quercetin, ascorbic acid/epicatechin, epicatechin/caffeic acid, and quercetin/epicatechin were tested as compared to the sum of the individual effects. Concerning the effects on LDL protein oxidation, the results from carbonyl content and the tryptophan fluorescence measurements showed that the combination of quercetin and caffeic acid revealed the strongest inhibitory effect (p < 0.001 carbonyl content; p < or = 0.002 tryptohan fluorescence) on protein oxidation which was higher than the effect of the single compounds. The results of the present study indicate that a combination of different antioxidants can be superior to the action of single antioxidants in protecting LDL lipid and protein moiety against oxidation. However, the substances may act by different antioxidative mechanisms, which are not necessarily complementary.

Quantitative Structure – Antioxidant Activity Relationships of Flavonoid Compounds

A quantitative structure-antioxidant activity relationship (QSAR) study of 36 flavonoids was performed using the partial least squares projection of latent structures (PLS) method. The chemical structures of the flavonoids have been characterized by constitutional descriptors, two-dimensional topological and connectivity indices. Our PLS model gave a proper description and a suitable prediction of the antioxidant activities of a diverse set of flavonoids having clustering tendency.

Structure–antioxidant activity relationships of flavonoids isolated from the resinous exudate of Heliotropium sinuatum

Relationships between the structural characteristics of flavonoids isolated from the resinous exudate of Heliotropium sinuatum and their antioxidant activity were studied. Radical formation energies, Δ H of dehydrogenation and spin densities were calculated using DFT methods (B3LYP/6-31G*). Results show that studied flavonoids can be divided into two sets according to their activity. It has been found that antioxidant activity depends both on substitution pattern of hydroxyl groups of the flavonoid skeleton and the presence of an unsaturation at the C2–C3 bond. A good tendency between Δ H of dehydrogenation and antioxidant activity was established.

Evaluation of the antioxidant activity of flavonoids by “ferric reducing antioxidant power” assay and cyclic voltammetry

Flavonoids, naturally occurring phenolic compounds, have recently been studied extensively for their antioxidant properties. The structure-antioxidant activity relationships (SAR) of flavonoids have been evaluated against different free radicals, but "ferric reducing antioxidant power" (FRAP) assay, which determines directly the reducing capacity of a compound, has not been used for this purpose. In this study, the antioxidant activities of 18 structurally different flavonoids were evaluated by FRAP assay modified to be used in 96-well microplates. Furthermore, their oxidation potentials were also measured, which were in the range of +0.3 V (myricetin) to +1.2 V (5-hydroxy flavone) and were in good agreement with FRAP assay results. Quercetin, fisetin and myricetin had the lowest oxidation potentials and appeared the most active compounds in FRAP assay and were 3.02, 2.52 and 2.28 times more active than Trolox, respectively. Indications were found that the o-dihydroxy structure in the B ring and the 3-hydroxy group and 2,3-double bond in the C ring give the highest contribution to the antioxidant activity.

Structure–antioxidant activity relationships of flavonoids isolated from different plant species

In the course of our phytochemical studies of different plants from developing countries we isolated and structurally characterized several flavonoid derivatives (compounds 1– 26), both aglycones and glycosides, typical of the species investigated. The aim of this study was to evaluate varieties of medicinal plants that were growing in developing countries, known in traditional medicine as anti-inflammatory remedies, with respect to their flavonoidic isolated constituents, assuming that their anti-inflammatory activity could be explained, at least in part, by the presence of antioxidant principles. The antioxidant activities of compounds 1– 26 were evaluated by measuring their ability to scavenge the radical cation 2,2′-azino- bis (3-ethylbenzothiazoline-6-sulfonate) (ABTS + ) and the superoxide anion, to inhibit β-carotene oxidation in a lipid micelle system, and to inhibit xanthine oxidase activity, showing some structure–activity relationships.

Plasma quercetin metabolites: structure–antioxidant activity relationships

We studied quercetin metabolism in rats to determine the nature and conjugation positions on the resulting metabolites and to evaluate their contribution to the antioxidant activity of plasma. HPLC analysis showed that quercetin is primarily metabolized to glucuronides and sulfoglucuronides and, to a minor extent, to sulfates. ESI-MS/MS studies confirmed these results and indicate that the most plausible positions for glucuronidation and sulfation are the hydroxyl groups located at positions 5 and 7, excluding the 3′-OH and 4′-OH groups. Plasma antioxidant status was significantly higher in animals to which quercetin was administrated, suggesting that quercetin metabolites can retain some antioxidant activity when the o-catechol group does not undergo conjugation reactions. It was also shown that plasma quercetin metabolites could compete in vivo with other molecules for peroxynitrite. These results enabled the establishment of quercetin metabolite structure–antioxidant activity relationships and, hence, to understand their contribution for the antioxidant potential of plasma.

Antioxidant activity of phenolic and related compounds: a density functional theory study on the O–H bond dissociation enthalpy

We report here on calculations at the hybrid DFT/HF (B3-LYP/6-31G(d, p)) level of the O–H bond dissociation enthalpy (O–H BDE) of phenylpropenoic acids (caffeic, ferulic, p-coumaric and cinnamic) and phenolic acids and related compounds (gallic, methylgallate, vanillic and gentisic) in order to gain insight into the understanding of structure–antioxidant activity relationships. The results were correlated and discussed mainly on the basis of experimental data in a companion work (Galato D, Giacomelli C, Ckless K, Susin MF, Vale RMR, Spinelli A. Antioxidant capacity of phenolic and related compounds: correlation among electrochemical, visible spectroscopy methods and structure-antioxidant activity. Redox Report 2001; 6: 243–250). The O–H BDE values showed remarkable dependence on the hydroxyl position in the benzene ring and the existence of additional interaction due to hydrogen bonding. For parent molecules, the experimental antioxidant activity (AA) order was properly obeyed only when intramolecular hydrogen bonding was present in the radicalized structures of o-dihydroxyl moieties. In structurally related compounds, excellent correlation with experimental data was in general observed (0.64 < ρ < 0.99). However, it is shown that excellent correlation can also be obtained for this series of compounds considering p-radicalized structures which were not stabilized by intramolecular hydrogen bonding, but this had no physical meaning. These findings suggested that the antioxidant activity evaluation of phenolic and related compounds must take into consideration the characteristics of each particular compound.

Commonly used food antioxidants: a comparative study in dispersed systems

Some commonly used antioxidants, namely BHA, BHT, TBHQ, α-tocopherol and caffeic acid were comparatively studied in phosphatidylcholine liposomes and in o/w emulsions. Trolox was included as reference. Oxidation was monitored at 37 °C by measuring peroxide formation. Low polarity and sometimes the molecular size seem to be the determining factors for an appreciable antioxidant performance. BHA and BHT were the most effective at the low levels of addition used. α-Tocopherol had an intermediate activity. The pro-/antioxidant behaviour of caffeic acid was concentration dependent. TBHQ activity was slightly better than that of caffeic acid and comparable with that of Trolox. The results add to knowledge for structure antioxidant activity relationships in various systems and may also have a practical outcome concerning the optimum levels of use.

Theoretical elucidation on structure–Antioxidant activity relationships for indolinonic hydroxylamines

Indolinonic hydroxylamines (IH), representing a new type of antioxidants, are comparative to α-tocopherol to protect lipids from oxidation. To elucidate the structure–activity relationship for IH, B3LYP/6-31G(d, p) method was employed to calculate the O–H bond dissociation enthalpy (BDE), a theoretical parameter to characterize the free radical scavenging activity. By constructing several model molecules, it was revealed that hydroxylamine was the key structural factor for this type of antioxidants, and substituents had little effect on the O–H BDE. If the NR of IH was substituted by O, its activity got lower.

Theoretical Elucidation of Structure-Antioxidant Activity Relationships for Thiazolidinone Derivatives

Thiazolidinone Derivatives (TD) are a novel class of calcium ion (Ca2+) antagonists possessing both Ca2+ overload inhibition and antioxidant activity. The free radical scavenging activity of TD play a key role in its cardioprotective processes. To elucidate the structure-antioxidant activity relationships (SAAR) for TD, a series of phenolic analogues of TD were constructed by adding various substituents to phenol step by step. And the theoretical parameter characterizing the free radical scavenging activity, O–H bond dissociation energy (BDE), was calculated for these phenols by quantum chemical method AM1/B3LYP/6-31G**. Thus, the contribution of each substituent to the O–H BDE was obtained. As a result, not only the SAAR for TD was explained, but also the understanding on TD's antioxidative mechanism was deepened.

ESR study on the structure–antioxidant activity relationship of tea catechins and their epimers

The purpose of this study is to examine the relationship between the free radical scavenging activities and the chemical structures of tea catechins ((−)-epigallocatechin gallate (EGCG), (−)-epigallocatechin (EGC) and (−)-epicatechin (EC)) and their corresponding epimers ((−)-gallocatechin gallate (GCG), (−)-gallocatechin (GC) and (+)-catechin ((+)-C)). With electron spin resonance (ESR) we investigated their scavenging effects on superoxide anions (O −· 2) generated in the irradiated riboflavin system, singlet oxygen( 1O 2) generated in the photoradiation–hemoporphyrin system, the free radicals generated from 2,2′-azobis(2-amidinopropane)hydrochloride (AAPH) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical. The results showed that the scavenging effects of galloylated catechins (EGCG and GCG) on the four free radicals were stronger than those of nongalloylated catechins (EGC, GC, EC, (+)-C), and the scavenging effects of EGC and GC were stronger than those of EC and (+)-C. Thus, it is suggested that the presence of the gallate group at the 3 position plays the most important role in their free radical-scavenging abilities and an additional insertion of the hydroxyl group at the 5′ position in the B ring also contributes to their scavenging activities. Moreover, the corresponding phenoxyl radicals formed after the reaction with O −· 2 were trapped by DMPO and the ESR spectra of DMPO/phenoxyl radical adducts were observed ( a N=15.6 G and a H β =21.5 G). No significant differences were found between the scavenging effects of the catechins and their epimers when their concentrations were high. However, significant differences were observed at relatively low concentrations, and the lower their concentrations, the higher the differences. The scavenging abilities of GCG, GC and (+)-C were stronger than those of their corresponding epimers (EGCG, EGC and EC). The differences between their sterical structures played a more important role in their abilities to scavenge large free radicals, such as the free radicals generated from AAPH and the DPPH radical, than to scavenge small free radicals, such as O −· 2 and 1O 2, especially in the case with EGCG and GCG with more bulky steric hindrance.

Estimation of fertility of human sperm treated with surfactants in vitro, using zona pellucida-free golden hamster eggs

Green tea catechins are potent antioxidant for prevention of various free radical-related diseases. Their antioxidant properties can be improved by encapsulation in cyclodextrins (CDs). Four inclusion complexes of β-CD with (–)-epicatechin (EC), (–)-epigallocatechin (EGC), (–)-epicatechin gallate (ECG) and (–)-epigallocatechin gallate (EGCG) have been investigated using single-crystal X-ray diffraction analysis combined with full geometry optimization by DFT/B3LYP calculation and the DPPH assay, aiming to deepen the understanding on their structure–antioxidant activity relationship. Scrutinizing the inclusion structures and conformational changes of the four encapsulated epicatechins reveals the common host–guest stabilization scheme and the epicatechin conformational flexibility facilitating the enhancement of activity. Thermodynamic stability order derived from DFT calculation in vacuum fairly agrees with the order of improved antioxidant capacity deduced from the DPPH assay, β-CD–EGCG > β-CD–ECG > β-CD–EGC ≈ β-CD–EC.