Maja Molnar

Synthesis and Antioxidant Activity of Some New Coumarinyl-1,3-Thiazolidine-4-ones

A series of Schiff’s bases (E)-N-2-aryliden-2-(4-methyl-2-oxo-2H-chromen-7-yloxy)acetohydrazides 2a-l and N-(2-(substituted phenyl)-4-oxo-thiazolidin-3-yl)-2-(4-methyl-2-oxo-2H-chromen-7-yloxy)acetamides 3a-l were synthesized and evaluated for their antioxidant activity by the phosphomolybdenum method. Most of the Schiff’s bases and thiazolidine-4-ones bearing two hydroxyl groups on the phenyl ring showed excellent antioxidant activity in comparison with ascorbic acid. Preliminary investigation on cytotoxic and antifungal activity was done on some representative samples.

4-Methyl-7-hydroxycoumarin antifungal and antioxidant activity enhancement by substitution with thiosemicarbazide and thiazolidinone moieties

According to literature data, thiosemicarbazide and thiazolidinone moieties should enhance biological properties of coumarin. Antioxidant, metal-chelating and antifungal activities of all compounds were investigated and compared to the activity of the starting material, 7-hydroxy-4-methylcoumarin, and were proven to possess potent antioxidant and antifungal activity. In general, thiosemicarbazides showed higher scavenging activity towards DPPH and galvinoxyl radicals than did 4-thiazolidinones and some of them had the same or even better activity than had ascorbic acid itself, depending on the free radical used. In antifungal activity tests towards four foodborne mycotoxigenic fungi, Aspergillus flavus, Aspergillus ochraceus. Fusarium graminearum and Fusarium verticillioides, coumarin derivatives were proven to possess a very high activity in terms of growth inhibition, depending on the fungi investigated. In general, 4-thiazolidinones showed better antifungal activity than did thiosemicarbazides. F. graminearum was the most susceptible to the compounds investigated and F. verticillioides was proven to be the most resistant. Two compounds, both coumarinyl thiosemicarbazides, were found to possess both antifungal and antioxidant activity which could be useful for applications in medicine, food industry and agriculture.

Design and Synthesis of Some New 1,3,4-Thiadiazines with Coumarin Moieties and Their Antioxidative and Antifungal Activity

A series of newly disubstituted (compounds 4a,b) and trisubstituted 1,3,4-thiadiazines 5a–l with various substituents was prepared utilizing different thiosemicarbazides and 3-α-bromoacetylcoumarins as starting compounds. The structures of the synthesized 1,3,4-thiadiazines are elucidated and confirmed utilizing the corresponding analytical and spectroscopic data. All of the new thiadiazine derivatives were tested for their antioxidant activity, employing different antioxidant assays (DPPH scavenging activity, iron chelating activity, power reducing activity). Compounds 5b, 5f, 5j and 4b were proven to be the best DPPH radical scavengers, while compounds 5h and 5j have shown the best iron chelating activity. Thiadiazine derivatives were also tested on their antifungal activity against four mycotoxicogenic fungi, Aspergillus flavus, A. ochraceus, Fusarium graminearum and F. verticillioides. The best antifungal against A. flavus was proven to be compound 5e, while compounds 4a and 5c were the best antifungals on A. ochraceus, and compound 5g showed the best antifungal activity on F. verticillioides.

Design and Synthesis of Some Thiazolidin-4-ones Based on (7-Hydroxy-2-oxo-2H-chromen-4-yl) Acetic Acid

(7-Hydroxy-2-oxo-2H-chromen-4-yl)-acetic acid methyl ester (1) upon reaction with ethyl bromoacetate furnishes (7-ethoxycarbonylmethoxy-2-oxo-2H-chromen-4-yl)-acetic acid methylester (2), which on treatment with 100% hydrazine hydrate yields (7-hydrazinocarbonylmethoxy-2-oxo-2H-chromen-4-yl)-acetic acid hydrazide (3). The condensation of compound 3 with different aromatic aldehydes afforded a series of [7-(arylidenehydrazinocarbonylmethoxy)-2-oxo-2H-chromen-4-yl]-acetic acid arylidene-hydrazide Schiff’s bases 4a-k. Cyclo-condensation of compounds 4a-k with 2-mercapto-acetic acid in N,N-dimethylformamide in the presence of anhydrous ZnCl2 affords N-(2-aryl-4-oxothiazolidin-3-yl)-2-(4-(2-aryl-4-oxothiazolidin-3-ylcarbamoyl)-methyl)-2-oxo-2H-chromen-7-yloxy)-acetamides 5a-k. Structure elucidation of the products has been accomplished on the basis of elemental analysis, IR, 1H-NMR and 13C-NMR data. Compounds 4a-k and 5a-k will be screened for their antibacterial activity against both Gram-positive and Gram-negative bacteria and the results reported elsewhere in due course.

Screening of Six Medicinal Plant Extracts Obtained by Two Conventional Methods and Supercritical CO2 Extraction Targeted on Coumarin Content, 2,2-Diphenyl-1-picrylhydrazyl Radical Scavenging Capacity and Total Phenols Content

Six medicinal plants Helichrysum italicum (Roth) G. Don, Angelica archangelica L., Lavandula officinalis L., Salvia officinalis L., Melilotus officinalis L., and Ruta graveolens L. were used. The aim of the study was to compare their extracts obtained by Soxhlet (hexane) extraction, maceration with ethanol (EtOH), and supercritical CO2 extraction (SC-CO2) targeted on coumarin content (by high performance liquid chromatography with ultraviolet detection, HPLC-UV), 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) scavenging capacity, and total phenols (TPs) content (by Folin–Ciocalteu assay). The highest extraction yields were obtained by EtOH, followed by hexane and SC-CO2. The highest coumarin content (316.37 mg/100 g) was found in M. officinalis EtOH extracts, but its SC-CO2 extraction yield was very low for further investigation. Coumarin was also found in SC-CO2 extracts of S. officinalis, R. graveolens, A. archangelica, and L. officinalis. EtOH extracts of all plants exhibited the highest DPPH scavenging capacity. SC-CO2 extracts exhibited antiradical capacity similar to hexane extracts, while S. officinalis SC-CO2 extracts were the most potent (95.7%). EtOH extracts contained the most TPs (up to 132.1 mg gallic acid equivalents (GAE)/g from H. italicum) in comparison to hexane or SC-CO2 extracts. TPs content was highly correlated to the DPPH scavenging capacity of the extracts. The results indicate that for comprehensive screening of different medicinal plants, various extraction techniques should be used in order to get a better insight into their components content or antiradical capacity.

Supercritical Extraction of Scopoletin from Helichrysum italicum (Roth) G. Don Flowers.

INTRODUCTION The increasing popularity of immortelle (Helichrysum italicum (Roth) G. Don) and its products, particularly in the cosmetic industry, is evident nowadays. This plant is a source of coumarins, especially scopoletin, which are highly soluble in supercritical CO2 . OBJECTIVE The objective of this study was to perform the supercritical CO2 extraction process of Helichrysum italicum flowers at different values of pressure and temperature and to optimise the extraction process using response surface methodology in terms of obtaining the highest extraction yield and yield of extracted scopoletin. METHODOLOGY Extraction was performed in a supercritical extraction system under different extraction conditions of pressure and temperature determined by central composite rotatable design. The mass of flowers in the extractor of 40 g, extraction time of 90 min and CO2 mass flow rate of 1.94 kg/h were kept constant during experiments. Antioxidant activity was determined using the DPPH (1,1-diphenyl-2-picrylhydrazyl) free radical scavenging assay method. Scopoletin concentration was determined by HPLC. RESULTS Changes in extraction conditions affect the extracting results remarkably. The greatest extraction yield (6.31%) and the highest yield of scopoletin (1.933 mg/100 g) were obtained under extraction conditions of 20 MPa and 40°C. Extracts have also proven to possess antioxidant activity (44.0-58.1% DPPH scavenging activity) influenced by both temperature and pressure applied within the investigated parameters. CONCLUSION The extraction conditions, especially pressure, exhibited significant influence on the extraction yield as well as the yield of extracted scopoletin and antioxidant activity of extracts. Copyright

Design, Synthesis and Characterization of Some Novel 3-Coumarinyl- 5-aryliden-1, 3-thiazolidine-2, 4-diones and Their Antioxidant Activity

In our effort to obtain biologically active compounds, new 3,5-disubstituted 1,3-thiazolidine-2,4- diones (5a - r) were synthesized. A series of 5-arylmethylidene-1,3-thiazolidine-2,4-diones (3a - r) were prepared by Knoevenagel reaction from 1,3-thiazolidine-2,4-dione (2) and appropriate aromatic aldehydes. Condensation of 3a - r with 7-hydroxy-4-bromomethyl-2-oxo-2H-chromene (1) afforded novel 3-(7-hydroxy-2-oxo-2H-chromen-4-ylmethyl)-5-arylidene-1,3-thiazolidine-2,4-diones 5a - r. Compounds 3a - r and 5a - r were evaluated for their antioxidant activity (DPPH free radical scavenging activity). Graphical Abstract Design, Synthesis and Characterization of Some Novel 3-Coumarinyl- 5-aryliden-1,3-thiazolidine-2,4-diones and Their Antioxidant Activity

Deep Eutectic Solvents as Convenient Media for Synthesis of Novel Coumarinyl Schiff Bases and Their QSAR Studies

Deep eutectic solvents, as green and environmentally friendly media, were utilized in the synthesis of novel coumarinyl Schiff bases. Novel derivatives were synthesized from 2-((4-methyl-2-oxo-2H-chromen-7-yl)oxy)acetohydrazide and corresponding aldehyde in choline chloride:malonic acid (1:1) based deep eutectic solvent. In these reactions, deep eutectic solvent acted as a solvent and catalyst as well. Novel Schiff bases were synthesized in high yields (65–75%) with no need for further purification, and their structures were confirmed by mass spectra, 1H and 13C NMR. Furthermore, their antioxidant activity was determined and compared to antioxidant activity of previously synthesized derivatives, thus investigating their structure–activity relationship utilizing quantitative structure-activity relationship QSAR studies. Calculation of molecular descriptors has been performed by DRAGON software. The best QSAR model (Rtr = 0.636; Rext = 0.709) obtained with three descriptors (MATS3m, Mor22u, Hy) implies that the pairs of atoms higher mass at the path length 3, three-dimensional arrangement of atoms at scattering parameter s = 21 Å−1, and higher number of hydrophilic groups (-OH, -NH) enhanced antioxidant activity. Electrostatic potential surface of the most active compounds showed possible regions for donation of electrons to 1,1-diphenyl-2-picryhydrazyl (DPPH) radicals.

Antidiabetic Effects of Aronia melanocarpa and Its Other Therapeutic Properties

Diabetes is a global pandemic which warrants urgent attention due to its rising prevalence and economic burden. Thus, many alternative therapies are being researched for antidiabetic properties, given the inefficacy of current medicinal treatments. From this perspective, Aronia melanocarpa or black chokeberry has been investigated for its therapeutic properties in many studies, especially for its ability to combat hyperglycemia-induced oxidative stress and the macrovascular complications of diabetes including cardiovascular disease. Though A. melanocarpa is native to the eastern areas of North America, it has been planted extensively in Europe and Asia as well. Several in vivo studies have displayed the antioxidant properties of A. melanocarpa berry juice and plant extract in rat models where oxidative stress markers were observed to have significant reductions. Some of the potent bioactive compounds present in the fruits and other parts of the plant were identified as (−)-epicatechin, chlorogenic acid, neochlorogenic acid, and cyanidin-3-galactoside. Overall, A. melanocarpa could be considered a good source of antioxidants which is effective in combating hyperglycemia-induced oxidative stress.

An Improved and Efficient N-acetylation of Amines Using Choline Chloride Based Deep Eutectic Solvents

An optimization of N-acetylation of various amines was performed in cholin chloride based deep eutectic solvents. First the raction was optimized regarding amine:acetic ratio and reaction time, on anthranilic acid. Then the optimizatoin was done regarding the best DES on anthranilic acid and 4-chloroaniline, where the best conditions were in combination of cholin chloride and urea or malonic acid. A series of amines was then acetylated under these conditions, in both solvents, giving an excellent results considering reaction times (10-60 min) and isolated yields up to 91%. Choline chloride based deep eutectic solvents were proven to be an excellent media for fast, selective and catalyst-free acetylation of amines.