Martina Danihelová

Antioxidant action and cytotoxicity on HeLa and NIH-3T3 cells of new quercetin derivatives

ABSTRACT Quercetin is a natural polyphenol with proven health beneficial activities. In this study 15 new quercetin derivatives were prepared with the aim to enhance their bioavailability. Modification of their physicochemical properties could herewith improve the action in cells. The prepared compounds were tested for their antioxidant and cytotoxic activity. The ability to scavenge free radicals as well as ferric reducing antioxidant power of the new derivatives was not better than that of unmodified quercetin. But for acetylated esters a better cytotoxic activity was found on human cervical cancer cells HeLa than for the initial molecule. The best effect revealed chloronaphtoquinone quercetin (IC50=13.2 μM). For this compound comparable cytotoxic action on non-cancer murine fibroblast cells was detected (IC50=16.5 μM). The obtained results indicate that appropriate lipophilization of the quercetin molecule could improve its cytotoxic action in cells, probably due to its enhanced bioavailability

Lipophilization of flavonoids for their food, therapeutic and cosmetic applications

Lipophilization of flavonoids for their food, therapeutic and cosmetic applications Flavonoids represent large group of plant pigments. These polyphenolic compounds may be found in the nature as active components of fruits, vegetables and other plants and derived products. Due to established biological effects they are attractive substances for many areas of human life. Many flavonoids are nowadays used in pharmaceutical, cosmetic and food preparations. Their practical applications are in most cases limited by low solubility and stability in lipophilic media. Chemical or enzymatic lipophilization of flavonoid skeleton may not only increase their solubility and stability in lipophilic environment but also their biological properties. This review summarizes current knowledge in this field.

Polyphenol fatty acid esters as serine protease inhibitors: a quantum-chemical QSAR analysis.

We investigated the ability of polyphenol fatty acid esters to inhibit the activity of serine proteases trypsin, thrombin, elastase and urokinase. Potent protease inhibition in micromolar range was displayed by rutin and rutin derivatives esterified with medium and long chain, mono- and polyunsaturated fatty acids (1e–m), followed by phloridzin and esculin esters with medium and long fatty acid chain length (2a–d, 3a–d), while unmodified compounds showed only little or no effect. QSAR study of the compounds tested provided the most significant parameters for individual inhibition activities, i.e. number of hydrogen bond donors for urokinase, molecular volume for thrombin, and solvation energy for elastase. According to the statistical analysis, the action of elastase inhibitors is opposed to those of urokinase and thrombin. Cluster analysis showed two groups of compounds: original polyphenols together with rutin esters with short fatty acid chain length and rutin esters with long fatty acid chain length.

FLAVONOID NATURAL SOURCES AND THEIR IMPORTANCE IN THE HUMAN DIET

Flavonoids as natural bioactive compounds are present in almost every sort of fruits, vegetables and from them derived products. Flavonols may be found mainly in fruits and vegetables, while flavones are abundant in herbs and spices. Rich natural sources of flavanols are tea, cocoa, grape seeds or apple skin. Flavanones are primarily found in a variety of citrus fruits and anthocyanidins in many coloured berries. Soy is rich in isoflavonoids. Average daily intake of flavonoids is approximately in the range of 150 to 300 mg. It strongly depends on individual, country and culture usages. In west countries main dietary sources of flavonoids consist of tea, wine and fruits, while in east countries there is consumed mainly soy with high isoflavonoid content. Many studies have shown, that intake of fruits and vegetables with high flavonoid content is associated with lowered risk of incidence of some diseases such as cardiovascular or cancer. These findings are attributed to experimentally confirmed biological effects of flavonoids - antioxidant, anti-inflammatory, anti-allergic, anticancer or cardioprotective. The final effect is however depending on their bioavailability, which is in the case of flavonoids not high, because in the nature dominating flavonoid glycosides can poorly penetrate through lipophilic cell membranes. Final effective molecules are flavonoid metabolites, that more or less retain their biological activities. doi: 10.5219/160

Inhibition of pathophysiological proteases with novel quercetin derivatives

Abstract Novel quercetin derivatives were prepared to change its physicochemical properties and effects on activity of proteolytic enzymes. For them preparation, the selective protection procedures some of the quercetin hydroxyl groups and acylation of the others with acylchlorides were used. The ability of these compounds to inhibit the activity of serine proteases e.g. trypsin, thrombin, urokinase and elastase was studied. In micromolar range, tested derivatives were the most potent inhibitors of thrombin. There was estimated better inhibition of thrombin for prenylated, acetylated, feruloyl and caffeoyl quercetin esters. Slight inhibitory effect of all quercetin derivatives on elastase was found. Among tested derivatives only diquercetin displayed better inhibiton. Trypsin and urokinase were inhibited by quercetin at comparable level. Slight improvement in inhibitory effect of trypsin and urokinase was seen for chloronaphtoquinone quercetin that revealed enhanced inhibiton of thrombin, too. However, no influence on elastase activity was determined for this compound. Obtained results indicate that certain modifications of quercetin structure could improve its biological properties.

Quantitative Structure-Antioxidant Activity Relationship of Quercetin and its New Synthetised Derivatives

Quantitative Structure-Antioxidant Activity Relationship of Quercetin and its New Synthetised Derivatives Interest in the biological activity of the flavonoids increases due to the potential health benefits of these polyphenolic components of foodstuff. Our research investigates biological properties of the flavonoids and their new synthetized derivatives, focuses on the relationship between their antioxidant activity and their chemical structures. Quantitative structure-activity relationship (QSAR) attempts to correlate chemical structure with biological activity using statistical approaches. It is the process by which chemical structure of a molecule is quantitatively correlated with a well defined process, such as biological activity, that can be expressed quantitatively as the concentration of a substance required to give a certain biological response. When physicochemical properties or structures are expressed by numbers, the mathematical relation can be formed between the two. The mathematical expression can then be used to predict the biological response of other chemical compounds. QSARs represent predictive models derived from application of statistical tools correlating antioxidant activity (including desirable therapeutic effect and undesirable side effects) of chemicals with descriptors representative of molecular structure and properties. Obtaining a good QSAR model depends on many factors, such as the quality of biological data, the choice of descriptors and statistical methods. Any QSAR modeling should ultimately lead to statistically robust models capable of making accurate and reliable predictions of biological activities of new untested compounds.