Three New Acrylic Acid Derivatives from Achillea mellifolium as Potential Inhibitors of Urease from Jack Bean and α-Glucosidase from Saccharomyces cerevisiae

(1) Background: Achillea mellifolium belongs to a highly reputed family of medicinal plants, with plant extract being used as medicine in indigenous system. However, limited data is available regarding the exploitation of the medicinal potential of isolated pure compounds from this family; (2) Methods: A whole plant extract was partitioned into fractions and on the basis of biological activity, an ethyl acetate fraction was selected for isolation of pure compounds. Isolated compounds were characterized using different spectroscopic techniques. The compounds isolated from this study were tested for their medicinal potential using in-vitro enzyme assay, coupled with in-silico studies; (3) Results: Three new acrylic acid derivatives (1–3) have been isolated from the ethyl acetate fraction of Achillea mellifolium. The characterization of these compounds (1–3) was carried out using UV/Vis, FT-IR, 1D and 2D-NMR spectroscopy (¹H-NMR, ¹³C-NMR, HMBC, NOESY) and mass spectrometry. These acrylic acid derivatives were further evaluated for their enzyme inhibition potential against urease from jack bean and α glucosidase from Saccharomyces cerevisiae, using both in-silico and in-vitro approaches. In-vitro studies showed that compound 3 has the highest inhibition against urease enzyme (IC₅₀ =10.46 ± 0.03 μΜ), followed by compound 1 and compound 2 with percent inhibition and IC₅₀ value of 16.87 ± 0.02 c and 13.71 ± 0.07 μΜ, respectively, compared to the standard (thiourea-IC₅₀ = 21.5 ± 0.01 μΜ). The investigated IC₅₀ value of compound 3 against the urease enzyme is two times lower compared to thiourea, suggesting that this compound is twice as active compared to the standard drug. On the other hand, all three compounds (1–3) revealed mild inhibition potential against α-glucosidase. In-silico molecular docking studies, in combination with MD simulations and free energy, calculations were also performed to rationalize their time evolved mode of interaction inside the active pocket. Binding energies were computed using a MMPBSA approach, and the role of individual residues to overall binding of the inhibitors inside the active pockets were also computed; (4) Conclusions: Together, these studies confirm the inhibitory potential of isolated acrylic acid derivatives against both urease and α-glucosidase enzymes; however, their inhibition potential is better for urease enzyme even when compared to the standard.     

A Novel One Pot Synthesis of o‐Nitrophenylacetic Acid and Unexpected p‐Nitrobenzoic Acid by HNO3‐Mediated CH2 Extrusion Reaction of Phenylacetic Acid

The HNO₃‐mediated CH₂ extrusion reactions of phenylacetic acid lead to one pot synthesis of unexpected commercially important product 4‐nitrobenzoic acid through the formation of 4‐nitrophenylacetic acid and 2‐nitrophenylacetic acid.     

Synthesis and characterization of PEGylated iron and graphene oxide magnetic composite for curcumin delivery

Nowadays, nanostructures have been given significant attention in medical and biological fields. Among these nanostructures, graphene oxide (GO) has been widely used in drug delivery systems, because of its unique properties, and the ability to connect to other nanostructures such as magnetic nanoparticles (NPs) as well as polymers by its functional groups. In this research, first, GO was prepared by exfoliating graphite according to the modified Hummer’s method, and then the Fe₃O₄ NPs were synthesized by a simple co-precipitation method on GO nanosheets. In the next step, with the help of the ethyl-3-(3-dimethylaminopropyl) carbodiimide/N-hydroxysuccinimide coupling reagents, the polyethylene glycol (PEG) polymer was bonded to the GO-Fe₃O₄ nanocomposite. Finally, anti-cancer drug, curcumin (Cur) was loaded onto the nanocomposite and the Cur loading ratio was measured at about 8%. The samples were evaluated using Fourier transform-infrared, differential scanning calorimtery, vibrating-sample magnetometry, atomic force microscopy and dynamic light scattering techniques. The results show that the prepared nanocomposite is an appropriate candidate for biomedical applications.     

Critical point approaches to Gradient-Type systems on the Sierpi\'{n}ski Gasket

We investigate the existence of multiple solutions for parametric quasi-linear systems of the gradient-type on the Sierpi\''{n}ski gasket. We give some new criteria to guarantee that the systems have at least three weak solutions by using a variational method and some critical points theorems due to Ricceri. We extend and improve some recent results. Finally, we give two examples to illustrate the main results.     

Anomalous flow behavior in closed and open thin walled nanochannels

Molecular dynamics simulations have been carried out to examine water flow in symmetric and asymmetric open and closed ends nanochannels with hydrophilic surfaces. The results are counterintuitive and the opposite of what is observed in macro-systems-closed channels fill faster with fluid than do their open counterparts. In addition, hybrid closed-open asymmetric channels fill up even faster. These results can be explained on the basis of the fluid-structure interaction that arises through the different vibrational behaviors of the surface molecules that are part of the wall forming these channels. Such effects are not expected to be of significance in macro-channels, and point to an important case where macro and nanochannels exhibit contrary behavior. Since these effects results from strong interactions between the fluid molecules and solid surface, one would not expect them with hydrophobic walls, and our simulations confirm such behavior.     

Synthesis of a Glyoxalase I Inhibitor from Streptomyces griseosporeus NIIDAet OGASAWARA

The pseudolactones 6 and 12 were prepared in a straightforward way from methyl α-D -glucopyranoside and methyl α-D -mannopyranoside, respectively. The pseudolactone 6 reacted with tert-butyl lithioacetate to give the protected, trihydroxylated cyclohexenone carboxylate 7 (51 %). The sterically hindered, L-ribo-configurated pseudolactone 12 reacted with diethyl ethylphosphonate and dimethyl methylphosphonate to give the protected trihydroxycyclohexenones 17 (49 %) and 18 (62 %), respectively. The hydroxymethylated cyclohexenone 21 was obtained from 18 by treatment with Me₂AlSPh and then formaldehyde, oxidation of the product 19 , and elimination. Deprotection of 21 gave 2 , identical with KD16-Ul. Esterification of 2 gave 1 , identical with the title compound. Alternatively, 1 was obtained in higher yields by esterification of 21 , followed by deprotection of the hydroxy groups. This synthesis gave 1 and 2 from methyl α-D -mannopyranoside in an overall yield of 18 and 20 %, respectively, confirming their absolute configuration.     

Effects of pyrolysis temperatures on the textural,magnetic, morphology,and catalytic properties of supported nickel nanoparticles

The development of base metal catalysts for industrially important reactions continues to be an important goal of catalysis research. Herein, the effects of pyrolysis temperature on the textural, structural, surface, magnetics properties and catalytic properties of silica-supported nickel nanoparticles (NiNPs) were thoroughly investigated. Mono-dispersed NiNPs encapsulated in graphitic shells were first successfully obtained and were characterized using a variety of methods such as BET surface area measurement, CO-pulse chemisorption, X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), high resolution transmission electron microscopy (HR-TEM), and superconducting quantum interference device (SQUID) measurement. The findings showed that all catalysts’ properties were considerably altered with change in pyrolysis temperature. Hydrogenation of diphenylacetylene was then selected as the model reaction for the evaluation of the catalytic performance of the graphitic-shelled NiNPs. After testing, pyrolysis of a nickel at 800 °C (catalyst A) displayed tremendous activity and selectivity to produce >94% of stilbene with selectivities of 99% for the Z-isomer.     

Protective Effects of Thymoquinone,an Active Compound of Nigella sativa,on Rats with Benzo(a)pyrene-Induced Lung Injury through Regulation of Oxidative Stress and Inflammation

Benzopyrene [B(a)P] is a well-recognized environmental carcinogen, which promotes oxidative stress, inflammation, and other metabolic complications. In the current study, the therapeutic effects of thymoquinone (TQ) against B(a)P-induced lung injury in experimental rats were examined. B(a)P used at 50 mg/kg b.w. induced lung injury that was investigated via the evaluation of lipid profile, inflammatory markers, nitric oxide (NO), and malondialdehyde (MDA) levels. B(a)P also led to a decrease in superoxide dismutase (SOD) (34.3 vs. 58.5 U/mg protein), glutathione peroxidase (GPx) (42.4 vs. 72.8 U/mg protein), catalase (CAT) (21.2 vs. 30.5 U/mg protein), and total antioxidant capacity compared to normal animals. Treatment with TQ, used at 50 mg/kg b.w., led to a significant reduction in triglycerides (TG) (196.2 vs. 233.7 mg/dL), total cholesterol (TC) (107.2 vs. 129.3 mg/dL), and inflammatory markers and increased the antioxidant enzyme level in comparison with the group that was administered B(a)P only (p < 0.05). B(a)P administration led to the thickening of lung epithelium, increased inflammatory cell infiltration, damaged lung tissue architecture, and led to accumulation of collagen fibres as studied through haematoxylin and eosin (H&E), Sirius red, and Masson’s trichrome staining. Moreover, the recognition of apoptotic nuclei and expression pattern of NF-κB were evaluated through the TUNEL assay and immunohistochemistry, respectively. The histopathological changes were found to be considerably low in the TQ-treated animal group. The TUNEL-positive cells increased significantly in the B(a)P-induced group, whereas the TQ-treated group showed a decreased apoptosis rate. Significantly high cytoplasmic expression of NF-κB in the B(a)P-induced group was seen, and this expression was prominently reduced in the TQ-treated group. Our results suggest that TQ can be used in the protection against benzopyrene-caused lung injury.