Organophosphorus chemistry,XII. Reaction of furil with alkyl phosphites and ylide-phosphoranes

Summary The reaction of furil (1) with trialkyl phosphites2 yielded caged phosphorane derivatives of types3a-c. Dry hydrogen chloride gas converted3a-c into the respectivea-hydroxyvinyl-phosphates8a-c which are equally produced by reacting furil with the appropriate dialkyl phosphite7. The reaction of furil with ylide-phosphoranes10 proceeded according to the Wittig reaction mechanism to give the respective ethylenes11a-c. The new compounds have been characterized by their spectroscopic data (IR, PMR,³¹P-NMR, MS) and elementary analyses.Dedicated to Prof. M. Sidky on the occasion of his 60th birthday     

Preparation of cellulose and cellulose derivative azo compounds

Wood pulp and cotton linter are the most common sources of cellulose forindustrial use. Methyl cellulose (MC) and cellulose sulfate (CS) were preparedusing bleached wood pulp and cotton linter. Coloured azo compounds were alsoprepared from coupling cellulose, wood pulp, MC and CS with aromatic diazoniumsalt. The presence of electron-releasing or withdrawing substituents affectedthe electrophilic substitution reaction. The produced azo compounds werecharacterized by FT-IR methodology, as well as mass spectrometry, in which thefunctional groups and the ion fragments of the products were analyzed.     

Brightly phosphorescent trinuclear copper(I) complexes of pyrazolates: substituent effects on the supramolecular structure and photophysics

Synthetic details, solid-state structures, and photophysical properties of a group of trimeric copper(I) complexes containing pyrazolate ligands are described. The reaction of copper(I) oxide and the fluorinated pyrazoles [3-(CF(3))Pz]H, [3-(CF(3)),5-(Me)Pz]H, and [3-(CF(3)),5-(Ph)Pz]H leads to the corresponding trinuclear copper(I) pyrazolates, {[3-(CF(3))Pz]Cu}(3), {[3-(CF(3)),5-(Me)Pz]Cu}(3), and {[3-(CF(3)),5-(Ph)Pz]Cu}(3), respectively, in high yield. The {[3,5-(i-Pr)(2)Pz]Cu}(3) compound was obtained by a reaction between [Cu(CH(3)CN)(4)][BF(4)], [3,5-(i-Pr)(2)Pz]H, and NEt(3). These compounds as well as {[3,5-(Me)(2)Pz]Cu}(3) and {[3,5-(CF(3))(2)Pz]Cu}(3) adopt trimeric structures with nine-membered Cu(3)N(6) metallacycles. There are varying degrees and types of intertrimer Cu...Cu interactions. These contacts give rise to zigzag chains in the fluorinated complexes, {[3-(CF(3))Pz]Cu}(3), {[3-(CF(3)),5-(Me)Pz]Cu}(3), {[3-(CF(3)),5-(Ph)Pz]Cu}(3), and {[3,5-(CF(3))(2)Pz]Cu}(3), whereas the nonfluorinated complexes, {[3,5-(Me)(2)Pz]Cu}(3) and {[3,5-(i-Pr)(2)Pz]Cu}(3) form dimers of trimers. Out of all the compounds examined in this study, {[3-(CF(3)),5-(Ph)Pz]Cu}(3) has the longest (3.848 Angstroms) and {[3,5-(Me)(2)Pz]Cu}(3) has the shortest (2.946 Angstroms) next-neighbor intertrimer Cu...Cu distance. The Cu...Cu separations within the trimer units do not vary significantly (typically 3.20-3.26 Angstroms). All of these trinuclear copper(I) pyrazolates show bright luminescence upon exposure to UV radiation. The luminescence bands are hugely red-shifted from the corresponding lowest-energy excitations, rather broad, and unstructured even at low temperatures, suggesting metal-centered emissions owing to intertrimer Cu...Cu interactions that are strengthened in the phosphorescent state. The {[3-(CF(3)),5-(Ph)Pz]Cu}(3) compound exhibits an additional highly structured phosphorescence with a vibronic structure corresponding to the pyrazolyl (Pz) ring. The luminescence properties of solids and solutions of the trimeric compounds in this study show fascinating trends with dramatic sensitivities to temperature, solvent, concentration, and excitation wavelengths.     

Limoniastrum monopetalum–Mediated Nanoparticles and Biomedicines: In Silico Study and Molecular Prediction of Biomolecules

An in silico approach applying computer-simulated models helps enhance biomedicines by sightseeing the pharmacology of potential therapeutics. Currently, an in silico study combined with in vitro assays investigated the antimicrobial ability of Limoniastrum monopetalum and silver nanoparticles (AgNPs) fabricated by its aid. AgNPs mediated by L. monopetalum were characterized using FTIR, TEM, SEM, and DLS. L. monopetalum metabolites were detected by QTOF–LCMS and assessed using an in silico study for pharmacological properties. The antibacterial ability of an L. monopetalum extract and AgNPs was investigated. PASS Online predictions and the swissADME web server were used for antibacterial activity and potential molecular target metabolites, respectively. Spherical AgNPs with a 68.79 nm average size diameter were obtained. Twelve biomolecules (ferulic acid, trihydroxy-octadecenoic acid, catechin, pinoresinol, gallic acid, myricetin, 6-hydroxyluteolin, 6,7-dihydroxy-5-methoxy 7-O-β-d-glucopyranoside, methyl gallate, isorhamnetin, chlorogenic acid, 2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-4-oxo-4H-chromen-3-yl 6-O-(6-deoxy-β-l-mannopyranosyl)-β-d-glucopyranoside) were identified. The L. monopetalum extract and AgNPs displayed antibacterial effects. The computational study suggested that L. Monopetalum metabolites could hold promising antibacterial activity with minimal toxicity and an acceptable pharmaceutical profile. The in silico approach indicated that metabolites 8 and 12 have the highest antibacterial activity, and swissADME web server results suggested the CA II enzyme as a potential molecular target for both metabolites. Novel therapeutic agents could be discovered using in silico molecular target prediction combined with in vitro studies. Among L. Monopetalum metabolites, metabolite 12 could serve as a starting point for potential antibacterial treatment for several human bacterial infections.     

Validated HPTLC and HPLC methods for determination of fluorometholone and sodium cromoglycate in presence of their impurities and degradation products; application to kinetic study and on rabbit aqueous humor

Fluorometholone (FLM) and Sodium Cromoglycate (CMG) are co-formulated in ophthalmic preparation and showed marked instability under different conditions. Two specific, sensitive and precise stability-indicating chromatographic methods have been developed and validated for their determination in the presence of their degradation products and FLM impurity. Ten components were efficiently separated by them. The first method was HPTLC-spectrodensitometry, where the separation was achieved using silica gel 60?F₂₅₄ HPTLC plates and developing system of ethyl acetate: methanol (9:1, v/v). The second method was a reversed phase HPLC associated with kinetic study of the degradation process and was successfully applied for determination of the studied compounds in spiked rabbit aqueous humor. The mobile phase was acetonitrile: methanol: 0.05?M potassium dihydrogenphosphate (0.1% trimethylamine); pH 2.5, adjusted with orthophosphoric acid (20: 30: 50, by volume). In both methods, the separated components were detected at 240?nm and system suitability was checked. Good correlation was obtained in the range of 0.10–24.00 and 0.20–48.00?µg band^?1, for FLM and CMG by HPTLC. While for HPLC, the linearity ranges from 0.01–50.00 and 0.05–50.00?µg?mL^?1 for both drugs. The methods were applied in pharmaceutical formulation, where they were compared to the reported method with no significant difference.     

Chromatographic determination of sulfasalazine and its active metabolites: greenness assessment and application to spiked human plasma

Green TLC-densitometric and RP-HPLC methods were developed and validated for the determination of the active prodrug sulfasalazine (SZ), its active metabolite mesalazine (MZ) and the major active metabolite of mesalazine, N-acetyl-5-aminosalicylic acid (AS). In the developed TLC-densitometric method, chromatographic separation was carried out on TLC silica gel plates 60 F₂₅₄ using a developing system consisting of ethyl acetate–methanol–ammonia solution 33% (8:2.5:0.3, by volume) and then scanning the separated bands at 215 nm using hydrochlorothiazide as an internal standard with linearity ranges of 0.4–3, 0.4–2.4 and 0.3–2 for SZ, MZ and AS, respectively. The developed RP-HPLC method depended on chromatographic separation using a C₁₈ column with a solvent mixture of methanol–aqueous acetic acid solution (pH 5) as a mobile phase with gradient elution mode and UV scanning at 243 nm using pyrazinamide as internal standard with linearity ranges of 5–50, 5–40, and 3–20 for SZ, MZ and AS, respectively. US Food and Drug Administration guidelines were followed during validation of the methods. The greenness of the developed methods was estimated using the greenness profile and the Eco-Scale approach. Both methods passed the four quadrants of the greenness profile and had Eco-Scale score ˃75, thus they were considered to be green according to these approaches.     

Phytochemical Profiling of Lavandula coronopifolia Poir. Aerial Parts Extract and Its Larvicidal,Antibacterial, and Antibiofilm Activity Against Pseudomonas aeruginosa

Infections associated with the emergence of multidrug resistance and mosquito-borne diseases have resulted in serious crises associated with high mortality and left behind a huge socioeconomic burden. The chemical investigation of Lavandula coronopifolia aerial parts extract using HPLC–MS/MS led to the tentative identification of 46 compounds belonging to phenolic acids, flavonoids and their glycosides, and biflavonoids. The extract displayed larvicidal activity against Culex pipiens larvae (LC₅₀ = 29.08 µg/mL at 72 h). It significantly inhibited cytochrome P-450 monooxygenase (CYP450), acetylcholinesterase (AChE), and carboxylesterase (CarE) enzymes with the comparable pattern to the control group, which could explain the mode of larvae toxification. The extract also inhibited the biofilm formation of Pseudomonas aeruginosa by 17–38% at different Minimum Inhibitory Concentrations (MICs) (0.5–0.125 mg/mL) while the activity was doubled when combined with ciprofloxacin (ratio = 1:1 v:v). In conclusion, the wild plant, L. coronopifolia, can be considered a promising natural source against resistant bacteria and infectious carriers.     

Facile synthesis of silver doped-copper oxide nano materials utilizing areca catechu (AC) leaf extract and their antidiabetic and anticancer studies

The present research highlights physical significance of green combination of metal oxide nanomaterials utilizing medicinal plant which has widely analyzed in different medical applications i.e., medicinal science, therapeutics. In this paper, we discussed environmentally benign approach for synthesizing silver doped copper oxide nanoparticles (Ag–CuO NPs) utilizing (ACLE). Scanning electron microscopy (SEM), X-ray diffraction (XRD), transmission electron microscopy (TEM) and energy dispersive spectroscopy (EDS) were utilized to confirm the size, crystalline structure and surface morphology of the obtained nanomaterials. The monoclinic crystalline structure of the Ag–CuO NPs as produced was revealed by XRD patterns. Morphological analysis disclosed the nano-based spherical configuration of Ag–CuO NPs, as well as their morphology and elemental composition. The anti-diabetic effect of Ag–CuO NPs was further investigated utilizing a yeast cell model and amylase inhibition. Here, a decrease in intracellular glucose and a delay in carbohydrate digestion indicate promising antidiabetic action. Furthermore, the prepared nanomaterial showed anticancer potential against the MCF-7 cancer cell line, with an IC ₅₀ value of 11.21 g/ml.     

Docking-based comparative intermolecular contacts analysis as new 3-D QSAR concept for validating docking studies and in silico screening: NMT and GP inhibitors as case studies

The significant role played by docking algorithms in drug discovery combined with their serious pitfalls prompted us to envisage a novel concept for validating docking solutions, namely, docking-based comparative intermolecular contacts analysis (dbCICA). This novel approach is based on the number and quality of contacts between docked ligands and amino acid residues within the binding pocket. It assesses a particular docking configuration on the basis of its ability to align a set of ligands within a corresponding binding pocket in such a way that potent ligands come into contact with binding site spots distinct from those approached by low-affinity ligands and vice versa. In other words, dbCICA evaluates the consistency of docking by assessing the correlation between ligands' affinities and their contacts with binding site spots. Optimal dbCICA models can be translated into valid pharmacophore models that can be used as 3-D search queries to mine structural databases for new bioactive compounds. dbCICA was implemented to search for new inhibitors of candida N-myristoyl transferase as potential antifungal agents and glycogen phosphorylase (GP) inhibitors as potential antidiabetic agents. The process culminated in five selective micromolar antifungal leads and nine GP inhibitory leads.     

Bioguided isolation of pentacyclic triterpenes from the leaves of Alstonia scholaris (Linn.) R. Br. growing in Egypt

Ethanolic and aqueous extracts of the leaves and flowers of Alstonia scholaris were evaluated for their antioxidant activity by investigating their effect on blood glutathione levels in alloxan-induced diabetic rats. The ethanolic extract of the leaves was the most active; therefore, its cytotoxicity against HepG2 cells was also tested. Promising GI?? values of 1.96, 4.34 and 4.65?μg?mL?1 were observed for the extract, its chloroform and ethyl acetate fractions, respectively. The chloroform active subfraction I (GI???=?2.97?μg?mL?1) yielded betulin (1), betulinic acid (2) and ursolic acid (3) upon purification. Compounds 1-3 were identified using spectroscopic techniques and by comparison with reported data. GLC of unsaponifiable and saponifiable fractions of the hexane extract revealed β-sitosterol (7.37%) and n-tetracosane (54.4%) to be the major sterol and hydrocarbon components, respectively. Linoleic acid (48.89%) was the predominant fatty acid.