The Potential of Parsley Polyphenols and Their Antioxidant Capacity to Help in the Treatment of Depression and Anxiety: An In Vivo Subacute Study

Depression and anxiety are major mental health problems in all parts of the world. These illnesses are associated with a number of risk factors, including oxidative stress. Psychotropic drugs of a chemical nature have demonstrated several side effects that elevated the impact of those illnesses. Faced with this situation, natural products appear to be a promising alternative. The aim of this study was to evaluate the anxiolytic and antidepressant effects of the Petroselinum sativum polyphenols in vivo, as well as its correlated antioxidant properties in vitro. Anxiolytic activity of the extract (50 and 100 mg/kg) was evaluated using the open field and the light-dark chamber tests, while the antidepressant activity was evaluated using the forced swimming test. The antioxidant activity of the extract was evaluated by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical test and the FRAP (iron-reducing capacity) test. The phenolic extract showed very powerful anxiolytic and antidepressant-like effects, especially at a dose of 100 mg/kg, decreasing the depressive behavior in mice (decreased immobility time) and also the anxiolytic behavior (tendency for discovery in the center and illuminated areas) better even than those of paroxetine and bromazepam (classic drugs) concomitant with those results the extract also showed an important antioxidant capacity. These preliminary results suggest that Petroselinum sativum exhibits anxiolytic and antidepressant potential for use as a complement or independent phytomedicine to treat depression and anxiety.     

Isolation,Structure Elucidation and In Silico Prediction of Potential Drug-Like Flavonoids from Onosma chitralicum Targeted towards Functionally Important Proteins of Drug-Resistant Bad Bugs

Admittedly, the disastrous emergence of drug resistance in prokaryotic and eukaryotic human pathogens has created an urgent need to develop novel chemotherapeutic agents. Onosma chitralicum is a source of traditional medicine with cooling, laxative, and anthelmintic effects. The objective of the current research was to analyze the biological potential of Onosma chitralicum, and to isolate and characterize the chemical constituents of the plant. The crude extracts of the plant prepared with different solvents, such as aqueous, hexane, chloroform_, ethyl acetate, and butanol, were subjected to antimicrobial activities. Results corroborate that crude (methanol), EtoAc, and n-C₆H₁₄ fractions were more active against bacterial strains. Among these fractions, the EtoAc fraction was found more potent. The EtoAc fraction was the most active against the selected microbes, which was subjected to successive column chromatography, and the resultant compounds 1 to 7 were isolated. Different techniques, such as UV, IR, and NMR, were used to characterize the structures of the isolated compounds 1–7. All the isolated pure compounds (1–7) were tested for their antimicrobial potential. Compounds 1 (4′,8-dimethoxy-7-hydroxyisoflavone), 6 (5,3′,3-trihydroxy-7,4′-dimethoxyflavanone), and 7 (5′,7,8-trihydroxy-6,3′,4′-trimethoxyflavanone) were found to be more active against Staphylococcus aureus and Salmonella Typhi. Compound 1 inhibited S. typhi and S. aureus to 10 ± 0.21 mm and 10 ± 0.45 mm, whereas compound 6 showed inhibition to 10 ± 0.77 mm and 9 ± 0.20 mm, respectively. Compound 7 inhibited S. aureus to 6 ± 0.36 mm. Compounds 6 and 7 showed significant antibacterial potential, and the structure–activity relationship also justifies their binding to the bacterial enzymes, i.e., beta-hydroxyacyl dehydratase (HadAB complex) and tyrosyl-tRNA synthetase. Both bacterial enzymes are potential drug targets. Further, the isolated compounds were found to be active against the tested fungal strains. Whereas docking identified compound 7, the best binder to the lanosterol 14α-demethylase (an essential fungal cell membrane synthesizing enzyme), reported as an antifungal fluconazole binding enzyme. Based on our isolation-linked preliminary structure-activity relationship (SAR) data, we conclude that O. chitralicum can be a good source of natural compounds for drug development against some potential enzyme targets.     

An Experimental and Computational Investigation Rules Out Direct Nucleophilic Addition on the N2 Ligand in Manganese Dinitrogen Complex [Cp(CO)2Mn(N2)]

We have re-examined the reactivity of the manganese dinitrogen complex [Cp(CO)₂Mn(N₂)] ( 1 , Cp=η⁵-cyclopentadienyl, C₅H₅) with phenylithium (PhLi). By combining experiment and density functional theory (DFT), we have found that, unlike previously reported, the direct nucleophilic attack of the carbanion onto coordinated dinitrogen does not occur. Instead, PhLi reacts with one of the CO ligands to provide an anionic acylcarbonyl dinitrogen metallate [Cp(CO)(N₂)MnCOPh]Li ( 3 ) that is stable only below −40 °C. Full characterization of 3 (including single crystal X-ray diffraction) was performed. This complex decomposes quickly above −20 °C with N₂ loss to give a phenylate complex [Cp(CO)₂MnPh]Li ( 2 ). The latter compound was erroneously formulated as an anionic diazenido compound [Cp(CO)₂MnN(Ph)=N]Li in earlier reports, ruling out the claimed and so-far unique behavior of the N₂ ligand in 1 . DFT calculations were run to explore both the hypothesized and the experimentally verified reactivity of 1 with PhLi and are fully consistent with our results. Direct attack of a nucleophile on metal-coordinated N₂ remains to be demonstrated.     

Electrochemical determination of sulfaguanidine using COOH-MWCNT coated GC electrode

The electrochemical behavior of sulfaguanidine was investigated in PBS buffer aqueous solutions. Cyclic voltammograms have shown that (1) the Sg provided a well-defined irreversible oxidation peak (2) the signal-to-background current ratio is 3 times higher at COOH-MWCNT coated GCE than that of bare GCE and (3) the modifying GCE surface by COOH-MWCNT led to a significant improvement (2.7 folds) of the electrochemical response. It has been shown that Sg oxidizes according to a diffusion-controlled mechanism. A linear calibration curve was obtained for the oxidation of Sg at 10–70 μM. The COOH-MWCNT coated GCE has also been successfully used for the determination of Sg in real samples.     

QSAR Modeling,Molecular Docking and Cytotoxic Evaluation for Novel Oxidovanadium(IV) Complexes as Colon Anticancer Agents

Four new drug-based oxidovanadium (IV) complexes were synthesized and characterized by various spectral techniques, including molar conductance, magnetic measurements, and thermogravimetric analysis. Moreover, optimal structures geometry for all syntheses was obtained by the Gaussian09 program via the DFT/B3LYP method and showed that all of the metal complexes adopted a square-pyramidal structure. The essential parameters, electrophilicity (ω) value and expression for the maximum charge that an electrophile molecule may accept (ΔN_max) showed the practical biological potency of [VO(CTZ)₂] 2H₂O. The complexes were also evaluated for their propensity to bind to DNA through UV–vis absorption titration. The result revealed a high binding ability of the [VO(CTZ)₂] 2H₂O complex with K_b = 1.40 × 10⁶ M⁻¹. Furthermore, molecular docking was carried out to study the behavior of the VO (II) complexes towards colon cancer cell (3IG7) protein. A quantitative structure–activity relationship (QSAR) study was also implemented for the newly synthesized compounds. The results of validation indicate that the generated QSAR model possessed a high predictive power (R² = 0.97). Within the investigated series, the [VO(CTZ)₂] 2H₂O complex showed the greatest potential the most selective compound comparing to the stander chemotherapy drug.     

Palladium-catalyzed addition of nitrogen pronucleophiles to alkylidenecyclopropanes

The inter- and intramolecular additions of cyclic amides (nitrogen pronucleophiles) to methylenecyclopropanes proceeded smoothly in the presence of catalytic amounts of Pd(PPh(3))(4), affording the corresponding hydroamination products in good to high yields with high regioselectivities. The ring opening of methylenecyclopropanes occurred at the distal position of the cyclopropane ring.     

Asymmetric Mannich reactions of beta-keto esters with acyl imines catalyzed by cinchona alkaloids

Cinchona alkaloids catalyze the enantioselective Mannich reaction of beta-keto esters with acyl aryl imines. The reaction requires 10 mol % of cinchonine or cinchonidine. The reaction products are obtained in good yields (81-99%), high enantioselectivities (80-96% ee), and in diastereoselectivities that range from 1:1 to >95:5. The cinchonine-catalyzed reaction provides access to highly functionalized building blocks used in the asymmetric synthesis of a dihydropyrimidone and beta-amino alcohol.     

New ent-kaurane diterpenoid dimer from Pulicaria inuloides

A new naturally occurring ent-kaurane diterpenoid dimer, 15β, 15′β-oxybis (ent-kaur-16-en-19-oic acid) (1) along with six known compounds, 15β-hydroxy-ent-kaur-16-en-19-oic acid (2), 15β-hydroxy-ent-kaur-16-en-19-oate-β-d-glucopyranoside (3), 6-hydroxykaempferol-3, 7-dimethyl ether (4), quercetagetin 3, 7, 3′-trimethyl ether (5), β-sitosterol (6) and β-sitosterol glucoside (daucosterol) (7) were isolated from the aerial parts of Pulicaria inuloides DC. Compounds 2–5 were isolated for the first time from genus Pulicaria. The structures of compounds 1–7 were established on the basis of extensive 1D and 2D NMR spectroscopic techniques in combination with ESI-MS. The antimicrobial activity of the isolated compounds was evaluated against Staphylococcus aureus, Escherichia coli and Candida albicans. Sulphorhodamine B cytotoxic assay against HepG2 (liver cancer) cell line and ABTS antioxidant assay were carried out.     

Polyvinylpyrrolidone Behavior in Water/Ethanol Mixed Solvents: Comparison of Modeling Predictions with Experimental Results

The objective of this work is to study the behavior of a neutral polymer, polyvinylpyrrolidone (PVP), in a mixture of water and ethanol. A comparison of the experimental results with a theoretical model of effective solvent interaction with polymer (ESIP) was made. To do so, dynamic light scattering experiments were used to measure the hydrodynamic radius of PVP (M _w = 3.6 × 10⁵ g·mol^?1) as a function of the ethanol fraction, x _A, in the medium at 25 °C. We show that the polymer adopts an ideal chain–globule–coil conformation transition as the ethanol molar fraction varies. This transition is attributed to the change of the solvent quality which results from water and ethanol complex formation. On the other hand, the ternary PVP/water/ethanol system was described by the ESIP model. From the polymer–effective solvent interaction, the second virial coefficient of the polymer/effective solvent and the preferential adsorption parameter were calculated. The obtained results are in agreement with the reported experiments.