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A Switch between Antioxidant and Prooxidant Properties of the Phenolic Compounds Myricetin, Morin, 3′,4′-Dihydroxyflavone, Taxifolin and 4-Hydroxy-Coumarin in the Presence of Copper(II) Ions: A Spectroscopic, Absorption Titration and DNA Damage Study

Fri, 01 Nov 2019 00:00:00 GMT

Title: A Switch between Antioxidant and Prooxidant Properties of the Phenolic Compounds Myricetin, Morin, 3′,4′-Dihydroxyflavone, Taxifolin and 4-Hydroxy-Coumarin in the Presence of Copper(II) Ions: A Spectroscopic, Absorption Titration and DNA Damage Study Authors: Jomová, Klaudia; Hudecová, Lenka; Lauro, Peter; Šimunková, Miriama; Alwasel, Saleh H.; Alhazza, Ibrahim M.; Valko, Marián Abstract: The beneficial effects of polyphenols, predominantly in the context of oxidative stress-related diseases such as cancer, cardiovascular diseases and neurological conditions including Alzheimer’s and Parkinson’s diseases, have been documented by a number of papers and reviews. The antioxidant/prooxidant properties of phenolic compounds are related mainly to the number and positions of hydroxyl groups and to their redox metal (Cu, Fe) chelating capacity. In this work we studied structurally distinct phenolic molecules such as myricetin, morin, 3′,4′-dihydroxy-flavone, taxifolin and 4-hydroxycoumarin, either alone or as interacting with Cu2+ ions. EPR and UV-Vis spectroscopy confirmed that the effective binding of cupric ions to phenolic compounds requires the presence of the 3-OH and 4-CO groups on the flavonoid C ring and unsaturated C2-C3 bond of the C-ring, which permits through-conjugation with the B-ring. An ABTS assay revealed that radical scavenging activities of phenolic compounds are related to their number of hydroxyl groups, planarity of the molecular skeleton, extent of delocalization and they decrease in the order: myricetin > morin > 3′,4′-dihydroxyflavone ~ 4-hydroxy coumarin > taxifolin. Absorption titrations indicate that copper ions can modulate the DNA binding affinity of flavonoids via the formation of their Cu-chelates. Gel electrophoresis measurements indicated that the protective effect of the phenolic compounds decreases in the order: 3′,4′-dihydroxyflavone > 4-OH coumarin > morin > taxifolin ~ myricetin. This can be explained by the fact that myricetin, taxifolin and morin form stable Cu(II) complexes capable of causing DNA damage via interaction with DNA and ROS formation via the Fenton reaction. Application of ROS scavengers revealed the formation of singlet oxygen, superoxide and hydroxyl radicals and their concerted synergistic effect on the DNA. The overall results suggest that the most pronounced DNA damage has been observed for flavonoids containing higher number of hydroxyl groups (including 3-OH group of the C ring), such as myricetin (six hydroxyl groups), morin and taxifolin (five hydroxyl groups) in the presence of Cu(II) ions. The proposed mechanism of action by which Cu(II) complexes of myricetin, morin and taxifolin interact with DNA predispose these substances to act as potential anticancer agents. The anticancer activity of phenolic compounds can be explained by their moderate prooxidant properties, which can boost ROS formation and kill cancer cells. Alternatively, slight prooxidant properties may activate antioxidant systems, including antioxidant enzymes and low molecular antioxidants such as glutathione and thus act as preventive anticancer agents. View Full-Text

Scalable Preparation of Enantioenriched (S)-5-methylhept-2-en-4-one. Synthesis and Aroma Properties of Achiral Analogues Thereof

Sun, 01 Dec 2019 00:00:00 GMT

Title: Scalable Preparation of Enantioenriched (S)-5-methylhept-2-en-4-one. Synthesis and Aroma Properties of Achiral Analogues Thereof Authors: Puchľová, Eva; Dendys, Michal; Špánik, Ivan; Szolcsányi, Peter Abstract: (S)-5-Methylhept-2-en-4-one is a key flavour compound in hazelnuts. We have performed its chiral-pool-based chemoenzymatic synthesis with 39% overall yield (73% ee). The four-step aldol-based sequence avoids the use of highly reactive and/or toxic reagents, does not require anhydrous conditions and uses only distillation as the purification method. Thus, such methodology represents a green and scalable alternative to only two stereoselective approaches towards this natural product known so far. In addition, we have designed and prepared a set of new (di)enones as achiral synthetic analogues of the title compound. The results of their sensory analyses clearly show that relatively minor structural changes of the natural molecule significantly alter its olfactory properties. Thus, simple (poly)methylation completely changes the original hazelnut aroma of (S)-5-methylhept-2-en-4-one and shifts the odour of its analogues to eucalyptus, menthol, camphor, and sweet aroma. View Full-Text

Effects of Terminal Substitution and Iron Coordination on Antiproliferative Activity of l‐Proline‐salicylaldehyde–Thiosemicarbazone Hybrids

Wed, 01 Nov 2017 00:00:00 GMT

Title: Effects of Terminal Substitution and Iron Coordination on Antiproliferative Activity of l‐Proline‐salicylaldehyde–Thiosemicarbazone Hybrids Authors: Milunović, Miljan N. M.; Dobrova, Aliona; Novitchi, Ghenadie; Gligorijević, Nevenka; Radulović, Siniša; Kožíšek, Jozef; Rapta, Peter; Enyedy, Eva A.; Arion, Vladimir B. Abstract: A series of five iron(III) complexes, namely [Fe(HL1)Cl2] (1), [Fe(HL2)Cl2]·1.6H2O (2·1.6H2O), [Fe(HL3)(MeOH)Cl2]·0.5H2O (3·0.5H2O), [Fe(HL4)(MeOH)Cl2]·0.5H2O (4·0.5H2O) and [Fe(HL4)(DMF)Cl2]·0.5Et2O·H2O (4′·0.5Et2O·H2O), where H2L1 = l-proline-salicylaldehyde–thiosemicarbazone (l-Pro-STSC), H2L2 = pyrrolidine-substituted l-Pro-STSC, H2L3 = phenyl-substituted l-Pro-STSC, and H2L4 = naphthyl-substituted l-Pro-STSC, have been synthesized. The two ligand precursors (H2L3 and H2L4) and iron complexes were characterized by elemental analysis, spectroscopic methods (UV/Vis, IR, and NMR), ESI mass spectrometry, cyclic voltammetry, and single-crystal X-ray crystallography (1–3 and 4′). Magnetic properties of the five-coordinate complex 2 and six-coordinate complex 4 have also been investigated. The antiproliferative activity of the organic hybrids and their iron(III) complexes have been studied in vitro in five human cell lines and one murine cancer cell line, namely HeLa (cervical cancer), FemX (melanoma), A549 (alveolar basal adenocarcinoma), LS-174 (colon cancer), MDA-MB-453 (breast cancer) and MS1 (transformed murine endothelial), as well as in human noncancerous fetal lung fibroblast cell line (MRC-5). According to the structure–activity relationship, introduction of aromatic groups such as phenyl or naphthyl enhances the cytotoxic potency of the hybrids in the following order H2L1 < H2L2 < H2L3 < H2L4. Coordination of the hybrids to iron(III) improves their antiproliferative activity in the majority of investigated cell lines with exception of H2L3 in LS-174, H2L4 in MS1, and both H2L3 and H2L4 in FemX cell lines, where an opposite effect was observed.

Comparison of different absorption corrections on the model structure of tetrakis(μ2-acetato)-diaqua-di-copper(II)

Sat, 01 Oct 2016 00:00:00 GMT

Title: Comparison of different absorption corrections on the model structure of tetrakis(μ2-acetato)-diaqua-di-copper(II) Authors: Kožíšková, Júlia; Hahn, Friedemann; Richter, Jens; Kožíšek, Jozef Abstract: Two different absorption correction methods were compared in order to find out which method is preferable to improve solving and refining a crystal structure. Experiments were performed on the crystal of a tetrakis(μ2-acetato)-diaqua-di-copper(II) complex. The first correction method used was the numerical absorption correction with the aid of a crystal-shape model, and the other was the semi-empirical one, applying scaling routines to the intensity data.