Distorted five-fold coordination of Cu2+(aq) from a Car-Parrinello molecular dynamics simulation

The solvation shell structure and dynamics of a single Cu2+ ion in a periodic box with 32 water molecules under ambient conditions has been investigated using Car-Parrinello molecular dynamics simulations in a time-window of 18 ps. Five-fold coordination with four equidistant equatorial water molecules at 2.00 A and one axial water molecule at 2.45 A from the Cu2+ ion is found. A "hole" without water molecules is found on the opposite side of the axial water. The ion-water bonding character for the equatorial water molecules is different from that of the axial water molecules, as shown by a localized orbital analysis of the electronic structure. Moreover, the calculated OD stretching vibrational band for the equatorial water molecules lies ca. 175 cm-1 below the axial-water band, in good agreement with experimental data. The equatorial-water band lies below, and the axial-water band above, the pure liquid D2O band, also in agreement with experimental data.     

Iphiona mucronata (Forssk.) Asch. & Schweinf. A Comprehensive Phytochemical Study via UPLC-Q-TOF-MS in the Context of the Embryo- and Cytotoxicity Profiles

Iphiona mucronata (Family Asteraceae) is widely distributed in the Eastern desert of Egypt. It is a promising plant material for phytochemical analysis and pharmacologic studies, and so far, its specific metabolites and biological activity have not yet been thoroughly investigated. Herein, we report on the detailed phytochemical study using UPLC-Q-TOF-MS approach. This analysis allowed the putative annotation of 48 metabolites belonging to various phytochemical classes, including mostly sesquiterpenes, flavonoids, and phenolic acids. Further, zebrafish embryotoxicity has been carried out, where 100 µg/mL extract incubated for 72 h resulted in a slow touch response of the 10 examined larvae, which might be taken as a sign of a disturbed peripheral nervous system. Results of in vitro testing indicate moderate cytotoxicity towards VERO, FaDu, and HeLa cells with CC₅₀ values between 91.6 and 101.7 µg/mL. However, selective antineoplastic activity in RKO cells with CC₅₀ of 54.5 µg/mL was observed. To the best of our knowledge, this is the first comprehensive profile of I. mucronata secondary metabolites that provides chemical-based evidence for its biological effects. A further investigation should be carried out to precisely define the underlying mechanisms of toxicity.     

Solanum elaeagnifolium Var. Obtusifolium (Dunal) Dunal: Antioxidant,Antibacterial, and Antifungal Activities of Polyphenol-Rich Extracts Chemically Characterized by Use of In Vitro and In Silico Approaches

The present work was designed to study the chemical composition and the antioxidant and antimicrobial properties of fruits (SFr) and leaf (SF) extracts from Solanum elaeagnifolium var. obtusifolium (Dunal) Dunal (S. elaeagnifolium). The chemical composition was determined using HPLC-DAD analysis. Colorimetric methods were used to determine polyphenols and flavonoids. Antioxidant capacity was assessed with DPPH, TAC, and FRAP assays. Antimicrobial activity was assessed using disk diffusion and microdilution assays against two Gram (+) bacteria (Staphylococcus aureus ATCC-6633 and Bacillus subtilis DSM-6333) and two Gram (-) bacteria (Escherichia coli K-12 and Proteus mirabilis ATCC-29906), while the antifungal effect was tested vs. Candida albicans ATCC-1023. By use of in silico studies, the antioxidant and antimicrobial properties of the studied extracts were also investigated. HPLC analysis showed that both fruits and leaf extracts from S. elaeagnifolium were rich in luteolin, quercetin, gallic acid, and naringenin. Both SFr and SF generated good antioxidant activity, with IC₅₀ values of 35.15 ± 6.09 μg/mL and 132.46 ± 11.73 μg/mL, respectively. The EC₅₀ of SFr and SF was 35.15 ± 6.09 μg/mL and 132.46 ± 11.73 μg/mL, respectively. SFr and SF also showed a good total antioxidant capacity of 939.66 ± 5.01 μg AAE/and 890.1 ± 7.76 μg AAE/g, respectively. SFr had important antibacterial activity vs. all tested strains—most notably B. subtilis DSM-6333 and E. coli, with MICs values of 2.5 ± 0.00 mg/mL and 2.50 ± 0.00 mg/mL, respectively. SFr demonstrated potent antifungal activity against C. albicans, with an inhibition diameter of 9.00 ± 0.50 mm and an MIC of 0.31 ± 0.00 mg/mL. The in silico approach showed that all compounds detected in SFr and SF had high activity (between −5.368 and 8.416 kcal/mol) against the receptors studied, including NADPH oxidase, human acetylcholinesterase, and beta-ketoacyl-[acyl carrier protein] synthase.     

The Ameliorative Effect of Empagliflozin in Vigabatrin-Induced Cerebellar/Neurobehavioral Deficits: Targeting mTOR/AMPK/SIRT-1 Signaling Pathways

Introduction. Vigabatrin (VGB) is an antiepileptic drug that acts to irreversibly inhibit the γ-aminobutyric acid (GABA) transaminase enzyme, elevating GABA levels. Broad studies have established that long-term treatment and/or high doses of VGB lead to variable visual defects. However, little attention has been paid to its other side effects, especially those demonstrating cerebellar involvement. Sodium glucose-linked co-transporter 2 (SGLT2) inhibitors are antidiabetic agents with protective effects far greater than expected based on their anti-hyperglycemic effect. Method. Our study herein was designed to investigate the possible ameliorative effect of empagliflozin, the SGLT2 inhibitors, in VGB-induced cerebellar toxicity. A total of 40 male Wistar rats were allocated equally into 4 groups: Group I: control group; Group II: VGB group; Group III empagliflozin treated VGB group; and Group IV: empagliflozin treated group. All groups were subjected to the detection of cerebellar messenger RNA gene expression of silent mating type information regulation 2 homolog 1 (SIRT1) and Nucleoporin p62 (P62). Mammalian target of rapamycin (mTOR), adenosine monophosphate-activated protein kinase (AMPK), and beclin1 levels were assessed by the ELISA technique while malondialdehyde (MDA) level and superoxide dismutase (SOD) activity were detected spectrophotometrically. Immuno-histochemical studies, focusing on glial fibrillary acidic protein (GFAP) and S100 were performed, and the optical color density and the mean area percentage of GFAP positive astrocytes and the number of S 100 positive cells were also counted. Results. Following empagliflozin treatment, we documented significant upregulation of both SIRT1 and P62 mRNA gene expression. Additionally, AMPK, Beclin1 levels, and SOD activity were significantly improved, while both mTOR and MDA levels were significantly reduced. Conclusions. We concluded for the first time that empagliflozin efficiently ameliorated the VGB-induced disrupted mTOR/AMPK/SIRT-1 signaling axis with subsequent improvement of the autophagy machinery and mitigation of the oxidative and inflammatory cellular environment, paving the way for an innovative therapeutic potential in managing VGB-induced neurotoxicity.     

Thermochemistry and kinetics of the aspect of diammonium hydrogen phosphate precipitation in phosphoric acid solution

Journal of Thermal Analysis and Calorimetry - The thermochemical and kinetic studies of diammonium hydrogen phosphate precipitation in phosphoric acid with ammonia were followed using a...     

Synthesis and antimicrobial evaluation of some novel dithiolane,thiophene, coumarin,and 2-pyridone derivatives

Novel 2-cyano-N-[1-(naphtha-2-yl)ethylidene] acetohydrazide 1 was utilized as key intermediate for the synthesis of some new dithiolane, thiophene, coumarin, 2-pyridone, and other related products containing a hydrazide moiety. Newly synthesized compounds were characterized by elemental analyses and spectral data (IR, ¹H NMR and mass spectra). The antimicrobial activity of the synthesized compounds was evaluated.     

Oxovanadium(IV) and ruthenium(II) carbonyl complexes of ONS‐donor ligands derived from dehydroacetic acid and dithiocarbazate: Synthesis,characterization, antioxidant activity,DNA binding and in vitro cytotoxicity

A series of new complexes of oxovanadium(IV) [VO(L)(B)] and ruthenium(II) [Ru(CO)(PPh₃)₂(L)] ( 1.1- 1.3,  2.1–2.3 ) (H₂L = dehydroacetic acid Schiff base of S‐methyldithiocarbazate, H₂smdha ( 1 ) or S‐benzyldithiocarbazate, H₂sbdha ( 2 ); B = 2,2′‐bipyridine (bpy) or 1,10‐phenanthroline (phen)) have been synthesized. The structure of these complexes was authenticated using elemental analyses and spectroscopic techniques, and their magnetic properties and electrochemical behaviour were studied. The molecular structures of oxovanadium(IV) complexes [VO(smdha)(bpy)]?CH₂Cl₂ ( 1.1 ) and [VO(sbdha)(phen)]?2H₂O ( 2.2 ) were confirmed using single‐crystal X‐ray crystallography. Analytical data showed that the ligands 1 and 2 are chelated to the metal centres in a bi‐negative tridentate fashion through azomethine N, thiol S and deprotonated hydroxyl group. The antioxidant activity of the synthesized compounds was tested against 2,2‐diphenyl‐1‐picrylhydrazyl) radical, which showed that the complexes demonstrate a better scavenging activity than their corresponding ligands. The cupric ion reducing antioxidant capacity method was also employed and the total equivalent antioxidant capacity values were found to be higher for the oxovandium(IV) complexes. DNA binding affinity of the compounds was determined using UV–visible and fluorescence spectra, revealing an intercalation binding mode. Higher cytotoxicity for the complexes compared to their ligands was found against human liver hepatocellular carcinoma (HepG2) and breast adenocarcinoma (MCF7) cell lines using MTT assay.     

Dual Amperometric Immunosensor for Improving Cancer Metastasis Detection by the Simultaneous Determination of Extracellular and Soluble Circulating Fraction of Emerging Metastatic Biomarkers

This paper reports the development of a dual immunosensor using magnetic microcarriers (MBs) and amperometric transduction at dual screen‐printed carbon electrodes (SPdCEs) for the simultaneous determination of two biomarkers: interleukin‐13 receptor α2 (IL‐13Rα2) and E‐cadherin (E‐CDH), with both extracellular and soluble fraction; oncogenic and tumor suppressor markers, respectively, of great relevance in metastatic processes. The implemented methodology involved the formation of sandwich‐type immunocomplexes using specific capture antibodies immobilized onto carboxylic acid magnetic microbeads (HOOC‐MBs), and biotinylated detector antibodies labeled with streptavidin?horseradish peroxidase conjugates (Strep‐HRP). The amperometric detection was performed by addition of hydrogen peroxide in the presence of hydroquinone (HQ) as the redox mediator. The dual immunosensing platform provided linear calibration ranges suitable for the determination of both biomarkers in liquid and solid clinical specimens as well as excellent selectivity against other cancer biomarkers. This simple handling dual bioplatform was applied to the determination of the soluble and extracellular fraction of the target biomarkers in serum and paraffined‐embedded tissues from colorectal cancer (CRC) patients diagnosed at different tumor grade. The obtained results reveal great potential of this configuration to improve the reliability in diagnosing metastatic CRC.     

Cu-Doped ZnO Nanoparticles for Non-Enzymatic Glucose Sensing

Copper-doped zinc oxide nanoparticles (NPs) Cu_xZn_1−xO (x = 0, 0.01, 0.02, 0.03, and 0.04) were synthesized via a sol-gel process and used as an active electrode material to fabricate a non-enzymatic electrochemical sensor for the detection of glucose. Their structure, composition, and chemical properties were characterized using X-ray diffraction (XRD), transmission electron microscopy (TEM), Fourier-transform infrared (FTIR) and Raman spectroscopies, and zeta potential measurements. The electrochemical characterization of the sensors was studied using cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), and differential pulse voltammetry (DPV). Cu doping was shown to improve the electrocatalytic activity for the oxidation of glucose, which resulted from the accelerated electron transfer and greatly improved electrochemical conductivity. The experimental conditions for the detection of glucose were optimized: a linear dependence between the glucose concentration and current intensity was established in the range from 1 nM to 100 μM with a limit of detection of 0.7 nM. The proposed sensor exhibited high selectivity for glucose in the presence of various interfering species. The developed sensor was also successfully tested for the detection of glucose in human serum samples.     

Mechanistic Insights into the Ameliorative Effect of Cichoriin on Diabetic Rats—Assisted with an In Silico Approach

Type 2 diabetes mellitus is considered to be a substantial socioeconomic burden worldwide on both patients and governments. Coumarins are biomolecules with a diversity of biological activities. The current investigation aimed to explore the ameliorative effects of cichoriin, which is a type of coumarin, on high-fat diet/streptozotocin (HFD/STZ)-induced diabetic rats. Methods: Rats were allocated into five groups. Group I was considered as the control group, while the other groups were HFD/STZ-induced diabetic rats. Group II was assigned as the diabetic control. Groups III and IV were treated with cichoriin (50 or 100 mg/kg, respectively). Group V received glibenclamide (5 mg/kg) (as a positive control). The blood glucose (BG), serum insulin, triglycerides (TG), total cholesterol (TC), total antioxidant capacity (TAC), catalase, hepatic superoxide dismutase (SOD) and content of malondialdehyde (MDA) were assessed. Histopathological and immunohistochemistry analysis of pancreatic tissue were performed. mRNA and protein expressions of GLUT4, AMPK, and PI3K were estimated. Results: Cichoriin treatment ameliorated HFD/STZ-induced diabetic conditions and mitigated the histopathological characteristics of the pancreas, as well as increasing pancreatic insulin expression. This decreased the levels of BG, TG, TC, and MDA and improved the TAC, catalase and SOD contents. Cichoriin demonstrated upregulation of mRNA and protein expressions of GLUT4, AMPK, and PI3K. The in silico binding of cichoriin with GLUT4, AMPK, and PI3K supported the possible current activities. Conclusion: Collectively, this work highlighted the potential role of cichoriin in mitigating HFD/STZ-induced diabetic conditions and showed it to be a valuable product.