Lucia Kovacikova

Aldose reductase inhibitory activity and antioxidant capacity of pomegranate extracts

Aldose reductase inhibitory activity and antioxidant capacity of pomegranate extracts The pomegranate, Punica granatum L., has been the subject of current interest as a medicinal agent with wide-ranging therapeutic indications. In the present study, pomegranate ethanolic seed and hull extracts were tested, in comparison with a commercial sample, for the inhibition of aldose reductase, an enzyme involved in the etiology of diabetic complications. In vitro inhibition of rat lens aldose reductase was determined by a conventional method. Pomegranate ethanolic hull extract and commercial pomegranate hull extract exhibited similar aldose reductase inhibitory activity characterized by IC50 values ranging from 3 to 33.3 μg/ml. They were more effective than pomegranate ethanolic seed extract with IC50 ranging from 33.3 to 333 μg/ml. Antioxidant action of the novel compounds was documented in a DPPH test and in a liposomal membrane model, oxidatively stressed by peroxyl radicals. All the plant extracts showed considerable antioxidant potential in the DPPH assay. Pomegranate ethanolic hull extract and commercial pomegranate hull extract executed similar protective effects on peroxidatively damaged liposomal membranes characterized by 10 < IC50 < 100 μg/ml. Pomegranate ethanolic seed extract showed significantly lower antioxidant activity compared to both hull extracts studied. Pomegranate extracts are thus presented as bifunctional agents combining aldose reductase inhibitory action with antioxidant activity and with potential therapeutic use in prevention of diabetic complications.

2-Chloro-1,4-naphthoquinone derivative of quercetin as an inhibitor of aldose reductase and anti-inflammatory agent

Abstract The ability of flavonoids to affect multiple key pathways of glucose toxicity, as well as to attenuate inflammation has been well documented. In this study, the inhibition of rat lens aldose reductase by 3,7-di-hydroxy-2-[4-(2-chloro-1,4-naphthoquinone-3-yloxy)-3-hydroxy-phenyl]-5-hydroxy-chromen-4-one (compound 1), was studied in greater detail in comparison with the parent quercetin (compound 2). The inhibition activity of 1, characterized by IC50 in low micromolar range, surpassed that of 2. Selectivity in relation to the closely related rat kidney aldehyde reductase was evaluated. At organ level in isolated rat lenses incubated in the presence of high glucose, compound 1 significantly inhibited accumulation of sorbitol in a concentration-dependent manner, which indicated that 1 was readily taken up by the eye lens cells and interfered with cytosolic aldose reductase. In addition, compound 1 provided macroscopic protection of colonic mucosa in experimental colitis in rats. At pharmacologically active concentrations, compound 1 and one of its potential metabolite 2-chloro-3-hydroxy-[1,4]-naphthoquinone (compound 3) did not affect osmotic fragility of red blood cells.

Screening for antiradical efficiency of 21 semi-synthetic derivatives of quercetin in a DPPH assay

Abstract The group of 21 novel semi-synthetic derivatives of quercetin was screened for the antiradical efficiency in a DPPH assay. The initial fast absorbance decrease of DPPH, corresponding to the transfer of the most labile H atoms, was followed by a much slower absorbance decline representing the residual antiradical activity of the antioxidant degradation products. Initial velocity of DPPH decolorization determined for the first 75-s interval was used as a marker of the antiradical activity. Application of the kinetic parameter allowed good discrimination between the polyphenolic compounds studied. The most efficient chloronaphthoquinone derivative (compound Ia) was characterized by antiradical activity higher than that of quercetin and comparable with that of trolox. Under the experimental conditions used, one molecule of Ia was found to quench 2.6±0.1 DPPH radicals.

Microwave assisted one pot synthesis of 7-substituted 2-(2-oxo-2H-chromen-3-yl)acetic acids as precursors of new anti-tumour compounds

Perkin condensation with subsequent intramolecular lactonisation as one pot syntheses of 2-(2-oxo-2H-chromen-3-yl)acetic acids VIIa-Xa has been studied. The required acids VIIa-Xa were prepared as precursors of recently discovered compounds possessing antineoplastic activities. Syntheses of VIIa-Xa were carried out using para substituted 2-hydroxybenzaldehydes II-VI, succinic acid anhydride, sodium succinate under thermal or microwave conditions. Significant shortening of the reaction time under microwave irradiation was observed (18–50 min instead of 1.5–5 h of heating). Microwave assisted reactions proceeded more smoothly to give higher yield of the required products VIIa-Xa (31–61 %) compared to those under classical thermal conditions e.g. 21.8 % for IXa (Hurenkamp et al., 2007). Seven reaction by-products were isolated and determined as 2H,2′H-3,3′-bichromene-2,2′-diones VIIb-Xb and (E)-3-(2-hydroxystyryl)-2H-chromen-2-ones VIIc-IXc.

Substituted pyridoindoles as biological antioxidants: drug design, chemical synthesis, and biological activity.

Great effort has been devoted to design and synthesize biologically active and pharmacologically acceptable antioxidants. Although a number of efficient antioxidant compounds have been designed, synthesized, and tested in animals, none of them have demonstrated sufficient efficacy in human clinical trials without undesirable side effects. Thus new pharmacologically applicable antioxidants have been sought for. Substituted pyridoindoles represent a broad spectrum of pharmacologically active substances including highly effective scavengers of reactive oxygen species. The hexahydropyridoindole scaffold represents a valuable lead with a great deal of knowledge on molecular mechanisms of free radical scavenging, on bioavailability and toxicity. Its modification may yield congeners tailored according to specific requirements for antiradical efficacy, lipophilicity, and basicity, meeting the aim of providing a pharmacologically practicable antioxidant drug as exemplified by the novel derivative SMe1EC2.