Validation of the Antioxidant and Enzyme Inhibitory Potential of Selected Triterpenes Using In Vitro and In Silico Studies,and the Evaluation of Their ADMET Properties

The antioxidant and enzyme inhibitory potential of fifteen cycloartane-type triterpenes’ potentials were investigated using different assays. In the phosphomolybdenum method, cycloalpioside D (6) (4.05 mmol TEs/g) showed the highest activity. In 1,1-diphenyl-2-picrylhydrazyl (DPPH*) radical and 2,2′-azino-bis(3-ethylbenzothiazoline)-6-sulfonic acid (ABTS) cation radical scavenging assays, cycloorbicoside A-7-monoacetate (2) (5.03 mg TE/g) and cycloorbicoside B (10) (10.60 mg TE/g) displayed the highest activities, respectively. Oleanolic acid (14) (51.45 mg TE/g) and 3-O-β-d-xylopyranoside-(23R,24S)-16β,23;16α,24-diepoxycycloart-25(26)-en-3β,7β-diol 7-monoacetate (4) (13.25 mg TE/g) revealed the highest reducing power in cupric ion-reducing activity (CUPRAC) and ferric-reducing antioxidant power (FRAP) assays, respectively. In metal-chelating activity on ferrous ions, compound 2 displayed the highest activity estimated by 41.00 mg EDTAE/g (EDTA equivalents/g). The tested triterpenes showed promising AChE and BChE inhibitory potential with 3-O-β-d-xylopyranoside-(23R,24S)-16β,23;16α,24-diepoxycycloart-25(26)-en-3β,7β-diol 2′,3′,4′,7-tetraacetate (3), exhibiting the highest inhibitory activity as estimated from 5.64 and 5.19 mg GALAE/g (galantamine equivalent/g), respectively. Compound 2 displayed the most potent tyrosinase inhibitory activity (113.24 mg KAE/g (mg kojic acid equivalent/g)). Regarding α-amylase and α-glucosidase inhibition, 3-O-β-d-xylopyranoside-(23R,24S)-16β,23;16α,24-diepoxycycloart-25(26)-en-3β,7β-diol (5) (0.55 mmol ACAE/g) and compound 3 (25.18 mmol ACAE/g) exerted the highest activities, respectively. In silico studies focused on compounds 2, 6, and 7 as inhibitors of tyrosinase revealed that compound 2 displayed a good ranking score (−7.069 kcal/mole) and also that the ΔG free-binding energy was the highest among the three selected compounds. From the ADMET/TOPKAT prediction, it can be concluded that compounds 4 and 5 displayed the best pharmacokinetic and pharmacodynamic behavior, with considerable activity in most of the examined assays.     

Metabolomics and Physiological Insights into the Ability of Exogenously Applied Chlorogenic Acid and Hesperidin to Modulate Salt Stress in Lettuce Distinctively

Recent studies in the agronomic field indicate that the exogenous application of polyphenols can provide tolerance against various stresses in plants. However, the molecular processes underlying stress mitigation remain unclear, and little is known about the impact of exogenously applied phenolics, especially in combination with salinity. In this work, the impacts of exogenously applied chlorogenic acid (CA), hesperidin (HES), and their combination (HES + CA) have been investigated in lettuce (Lactuca sativa L.) through untargeted metabolomics to evaluate mitigation effects against salinity. Growth parameters, physiological measurements, leaf relative water content, and osmotic potential as well as gas exchange parameters were also measured. As expected, salinity produced a significant decline in the physiological and biochemical parameters of lettuce. However, the treatments with exogenous phenolics, particularly HES and HES + CA, allowed lettuce to cope with salt stress condition. Interestingly, the treatments triggered a broad metabolic reprogramming that involved secondary metabolism and small molecules such as electron carriers, enzyme cofactors, and vitamins. Under salinity conditions, CA and HES + CA distinctively elicited secondary metabolism, nitrogen-containing compounds, osmoprotectants, and polyamines.     

Simulation of conversion profiles and temperature distributions within dimethacrylate thick material during photopolymerization

Photoinitiated polymerization of multifunctional monomers is an usual method to prepare highly crosslinked networks which have a wide variety of applications. This method leads to high reaction rates and the resulting exothermic effect of this reaction can be the cause of defects in the final material. The heterogeneities alter greatly the physical properties of ultimate products, particularly the optical ones, what causes problems in the design of thick and optically perfect materials. The knowledge of the conversion profile and the temperature distribution within the material during the photopolymerization is useful for the process optimization. Unfortunately, these parameters cannot be measured during the process. Thus, we decided to simulate them. Firstly, the necessary parameters (like conversion and reaction rate) were measured on thin material in isothermal conditions by photocalorimetry. Secondly, these kinetic data were used in a computational calculation to obtain the conversion profile and the temperature distribution within dimethacrylate thick material. The calculated temperature and conversion-time curves are in good agreement with the experimental curves determined under the same conditions.     

Electrical and optical properties of chalcopyrite compounds

Optical and electrical properties of Zn- and Cd-modified Cu₂SnSe₄ amorphous films have been studied. The results show that Zn and Cd incorporation decreases the thermal activation energy, the pre-exponential factor and the optical gap. Variation in the refractive index and extinction coefficient with the wavelength has been also reported. The relations between the optical gap and the chemical composition in the investigated films have been discussed in terms of the average heat of atomization. The effect of γ-radiation up to 71.25 Mrad dose on the optical gap was also studied.     

Synthesis and characterization of copper(II), cobalt(II), nickel(II), and iron(III) complexes with two diamine Schiff bases and catalytic reactivity of a chiral diamine cobalt(II) complex

New transition metal complexes of Co(II), Cu(II), Ni(II), and Fe(III) of the ligands 6,6′-(1E,1′E)-(4,5-dimethyl-1,2-phenylene)bis(azan-1-yl-1-ylidene)bis(methan-1-yl-1-ylidene)bis(7-hydroxy-5-methoxy-2-methyl-4H-chromen-4-one) H₂L¹ and 6,6’-(1E,1′E)-cyclohexane-1,2-diylbis(azan-1-yl-1-ylidene)bis(methan-1-yl-1-ylidene)bis(7-hydroxy-5-methoxy-2-methyl-4H-chromen-4-one) H₂L² have been prepared and characterized using physio-chemical and spectroscopic methods. The results obtained for the complexes indicated that the geometries of the metal centres are either square planar or octahedral. Cyclopropanation reactions of unactivated olefins by ethyldiazoacetate (EDA) in the presence of [L¹Cu]·H₂O, [L²Cu]·2H₂O and [L²*Co]·2H₂O as catalysts were examined. The results showed that only [L²*Co]·2H₂O can act as a catalyst for the cyclopropanation reaction of unactivated olefins with very high selectivity (up to 99% based on EDA).     

Fluorescence Study on the Interaction Between Hypericin and Lens Protein "α-Crystallin"

Hypericin has been reported as a potent photosensitizing agent exhibiting antiviral, antibacterial, antineoplastic activities. Although its photophysics and mode of action are strongly modulated by the binding protein, detailed information about its mechanism of interaction with possible cellular targets, including proteins, is still lacking. Previous in vitro studies demonstrated that hypericin can be uptaken by intact lens and is able to bind to the major lens protein "α-crystallin." In this study, the mechanism of interaction of this potent drug with α-crystallin was studied using the chemical denaturant guanidine hydrochloride (GdnHCl) and the hydrophobic surface probe, 8-anilino-1-naphthalenesulfonic acid (ANS). Fluorescence measurements showed that the increased exposure of tryptophan resulting from partial unfolding of α-crystallin incubated with 1.0 mol L⁻¹ of GdnHCl corresponds to the maximum accessibility of hydrophobic sites to ANS at the same GdnHCl concentration. Interestingly at this additional hydrophobicity of the protein, hypericin exhibited its maximum fluorescence intensity. This in vitro study implied that hydrophobic sites of α-crystallin play a significant role in its interaction with hypericin. The binding between α-crystallin and hypericin was found to be enhanced by partial perturbation of the protein.     

Development and Validation of HPLC,TLC and Derivative Spectrophotometric Methods for the Analysis of Ezetimibe in the Presence of Alkaline Induced Degradation Products

Reversed phase‐high performance liquid chromatography (RP‐HPLC), thin layer chromatography (TLC) densitometry and first derivative spectrophotometry (1D) techniques are developed and validated as a stability‐indicating assay of ezetimibe in the presence of alkaline induced degradation products. RP‐HPLC method involves an isocratic elution on a Phenomenex Luna 5μ C₁₈ column using acetonitrile: water: glacial acetic acid (50:50:0.1 v/v/v) as a mobile phase at a flow rate of 1.5 mL/min. and a UV detector at 235 nm. TLC densitometric method is based on the difference in Rf‐values between the intact drug and its degradation products on aluminum‐packed silica gel 60 F₂₅₄ TLC plates as stationary phase with isopropanol: ammonia 33% (9:1 v/v) as a developing mobile phase. On the fluorescent plates, the spots were located by fluorescence quenching and the densitometric analysis was carried out at 250 nm. Derivative spectrophotometry, the zero‐crossing method, ezetimibe was determined using first derivative at 261 nm in the presence of its degradation products. Calibration graphs of the three suggested methods are linear in the concentration ranges 1–10 mcg/mL, 0.1–1 mg/mL and 1–16 mcg/mL with a mean percentage accuracy of 99.05 ± 0.54%, 99.46 ± 0.63% and 99.24 ± 0.82% of bulk powder, respectively. The three proposed methods were successfully applied for the determination of ezetimibe in raw material and pharmaceutical dosage form; the results were statistically analyzed and compared with those obtained by the reported method. Validation parameters were determined for linearity, accuracy and precision; selectivity and robustness and were assessed by applying the standard addition technique.     

Multiplicity of solutions for elliptic quasilinear equations with critical exponent on compact manifolds

This paper deals with some perturbation of the so-called generalized prescribed scalar curvature type equations on compact Riemannian manifolds; these equations are nonlinear, of critical Sobolev growth, and involve the p-Laplacian. Sufficient conditions are given to have multiple positive solutions.