Neda Niciforovic

In vitro antioxidant activity of selected 4-hydroxy-chromene-2-one derivatives-SAR, QSAR and DFT studies.

The series of fifteen synthesized 4-hydroxycoumarin derivatives was subjected to antioxidant activity evaluation in vitro, through total antioxidant capacity, 1,1-diphenyl-2-picryl-hydrazyl (DPPH), hydroxyl radical, lipid peroxide scavenging and chelating activity. The highest activity was detected during the radicals scavenging, with 2b, 6b, 2c, and 4c noticed as the most active. The antioxidant activity was further quantified by the quantitative structure-activity relationships (QSAR) studies. For this purpose, the structures were optimized using Paramethric Method 6 (PM6) semi-empirical and Density Functional Theory (DFT) B3LYP methods. Bond dissociation enthalpies of coumarin 4-OH, Natural Bond Orbital (NBO) gained hybridization of the oxygen, acidity of the hydrogen atom and various molecular descriptors obtained, were correlated with biological activity, after which we designed 20 new antioxidant structures, using the most favorable structural motifs, with much improved predicted activity in vitro.

An efficient synthesis and antioxidant properties of novel imino and amino derivatives of 4-hydroxy coumarins.

Series of imino and amino derivatives of 4-hydroxy coumarins were synthesized via conventional and microwave promoted procedure and evaluated for antioxidant potential through different in vitro models such as (DPPH) free radical scavenging activity, linoleic acid emulsion model system, reducing power assay and phosphomolybdenum method. All prepared compounds possess good antioxidant activity and among them p-nitro-phenyl derivative 6c with IC50 at 25.9 μM possesses radical scavenging activity which is comparable to standard BHT, while the best reducing power was observed in a case of benzyl amino compound 8c (RP50 255.6 μM). Also, observed data indicated that compounds may serve as inhibitors of lipid peroxidation process.

Synthesis and Molecular Descriptor Characterization of Novel 4-Hydroxy-chromene-2-one Derivatives as Antimicrobial Agents

Several novel 4-hydroxy-chromene-2-one derivatives 2b-16b were easily prepared through condensation reactions with microwave heating and characterized by elemental analysis, IR, 1H-NMR and mass spectrometry. Geometry optimization of these compounds was executed by PM3, PM5 and Minimize Energy methods to describe them via molecular descriptors. The antimicrobial activity of the synthesized compounds was evaluated against different microbial strains using two different methods: the diffusion method and the micro-dilution method. All data indicated that the products possess antimicrobial activity which depends on the nature of substituent attached to the benzopyran moiety. In general, after 24 h the MIC values of most tested coumarins was 0.13 mg/mL, but compounds 1 and 6b displayed the strongest antimicrobial activity on the tested cultures of bacteria after 48 h. Compound 13b has the strongest growth inhibitory potential on fungus C. albicans, tested by diffusion method, with an inhibition zone of 30-37 mm at a concentration of 150 µg/mL. The conclusion of this experiment is that the synthesized compounds have varied and different influence on different classes of bacteria and the fungus C. albicans.

TOTAL PHENOLIC CONTENT, FLAVONOID CONCENTRATIONS AND ANTIOXIDANT ACTIVITY, OF THE WHOLE PLANT AND PLANT PARTS EXTRACTS FROM TEUCRIUM MONTANUM L. VAR. MONTANUM, F. SUPINUM (L.) REICHENB.

ABSTRACT The aim of this study was to determine the total phenolic content, concentrations of flavonoids and in vitro antioxidant activity of twenty different extracts from the plant and plant parts (leaves, flowers and stems) of Teucrium montanum L. var. montanum, f. supinum (L.) Reichenb. The total phenolic content in the extracts was determined using Folin-Ciocalteu reagent and their amounts ranged between 8.33 to 169.06 mg GA/g. The concentrations of flavonoids in plant extracts varied from 3.96 to 88.31 mg RU/g. Antioxidant activity was analyzed in vitro using DPPH reagent, activity expressed as IC50 and obtained results ranged from 29.41 to 2408.47 μg/mL. Parallel to the analysis of T. montanum, Ginkgo biloba L. and Green tea (Camellia sinensis (L.) Kuntze) extracts were analyzed for comparison, and the results indicated that some extracts of T. montanum were equal in activity with Ginkgo or Green tea and some appeared to have greater activity. Based on these results of investigation, it could be concluded that T. montanum is a rich source of phenolic compounds as natural antioxidans of high value.

Antimicrobial activity of the essential oil obtained from roots and chemical composition of the volatile constituents from the roots, stems, and leaves of Ballota nigra from Serbia.

The chemical composition of essential oils obtained from the roots, stems, and leaves of Ballota nigra, growing in Serbia, was investigated by gas chromatography/mass spectrometry analyses. Kovats indices, mass spectra, and standard compounds were used to identify a total of 115 individual compounds. The plant produces two types of essential oils. Oils derived from stems and leaves were sesquiterpene rich (78.17% and 88.40%, respectively), containing principally beta-caryophyllene, germacrene D, and alpha-humulene, present in appreciable amounts. In contrast, oil derived from the root was dominated by p-vinylguiacol (9.24%), borneol (7.51%), myrtenol (7.13%), trans-pinocarveol (5.22%), pinocarvone (4.37%), 2-methyl-3-phenylpropanal (4.32%), and p-cymen-8-ol (4.30%). Essential oil obtained from the roots was evaluated for the antimicrobial activity against seven bacterial species and one fungi.

Biochemical and pharmacological evaluation of 4-hydroxychromen-2-ones bearing polar C-3 substituents as anticoagulants.

The objective of this study was to investigate in vitro and in vivo anticoagulant activity of sixteen 4-hydroxycoumarin derivatives bearing polar C-3 scaffolds. The activity was evaluated by measuring prothrombin time. Enhanced anticoagulant activity in vitro was observed for all tested compounds. Upon successive administration of 0.5 mg/kg of body weight to adult Wistar rats, over a period of five days, four derivatives (2b, 4c, 5c and 9c) presented anticoagulant activity in vivo. The most active compound was 2b, with PT = 30.0 s. Low or non-toxic effects in vivo were determined based on the catalytic activity of liver enzymes and the concentration of bilirubin, iron and proteins. Metabolic pathways of the most active compounds in vivo were determined after GC/MS analysis of collected rat urine samples. The excretion occurs by glucuronidation of 7-hydroxy forms of tested derivatives. In vivo results were described using PLS-based CoMFA and CoMSIA 3D-QSAR studies, which showed CoMFA-SE (q(2) = 0.738) and CoMSIA-SEA (q(2) = 0.763) to be the statistically most relevant models. Furthermore, molecular docking and DFT mechanistic studies performed on the rat VKORC1 homology model revealed interactions between the 4-OH coumarin group in the form of phenolic anion and the Cys135 catalytic site in the transition state.

Antioxidant Activity, Phenol and Flavonoid Contents of Different Teucrium Chamaedrys L. Exstracts

ABSTRACT The paper presents the results of antioxidant activity of water, methanolic, ethyl-acetate, acetone and petroleum ether extract from plant species Teucrium chamaedys L. (Lamiaceae). Antioxidative activity was determined in vitro, using the DPPH reagent by spectrophotometric method. Experimental values are expressed as IC50 values (mg/ml), and show that the tested extracts have high antioxidant activities, which range in scope from 341.08 mg/ml to 29.46 mg/ml. In the tested extracts of plant species Teucrium chamaedys L. quantitative composition of total phenols and flavonoids were determined by spectrophotometric method. Total phenols determined by Folin-Ciocalteu reagent and their amounts in the range of 30.39 mg/g to 169.50 mg/g (expressed as gallic acid equivalent, mg GA/g of extract). The amounts of flavonoids in plant extracts of Teucrium chamaedys L. are in the range of 16.67 mg/g to 87.17 mg/g (expressed as rutin equivalent, mg RU/g of extract).

A Kinetic Approach in the Evaluation of Radical-Scavenging Efficiency of Sinapic Acid and Its Derivatives

A kinetic approach was used to determine the radical scavenging activities of sinapic acid and its derivatives: sinapine, 4-vinylsyringol, syringic acid, syringaldehyde, and ethyl, propyl and butyl sinapate. The responses were expressed as rates of 2,2-diphenyl-1-picrylhydrazyl radical (DPPH˙) scavenging (RS), superoxide radical (O2˙−) scavenging (RFF), and β-carotene bleaching in the emulsion system (RB). For RS and RB, the esters of sinapic acid showed the highest responses while, for RFF, this was seen for syringic acid. The effectiveness of the selected compounds for scavenging these free radicals was also determined at a fixed endpoint. The early response parameters were demonstrated to be good discriminators in assessing differences for antioxidants with comparable fixed endpoint activity. The primary feature that ranks the kinetic data and the endpoint determinations is interpreted in terms of the mechanisms of the reactions involved in each of the assays conducted.