Multi-Targeted Molecular Docking,Pharmacokinetics, and Drug-Likeness Evaluation of Okra-Derived Ligand Abscisic Acid Targeting Signaling Proteins Involved in the Development of Diabetes

Diabetes mellitus is a global threat affecting millions of people of different age groups. In recent years, the development of naturally derived anti-diabetic agents has gained popularity. Okra is a common vegetable containing important bioactive components such as abscisic acid (ABA). ABA, a phytohormone, has been shown to elicit potent anti-diabetic effects in mouse models. Keeping its anti-diabetic potential in mind, in silico study was performed to explore its role in inhibiting proteins relevant to diabetes mellitus- 11β-hydroxysteroid dehydrogenase (11β-HSD1), aldose reductase, glucokinase, glutamine-fructose-6-phosphate amidotransferase (GFAT), peroxisome proliferator-activated receptor-gamma (PPAR-gamma), and Sirtuin family of NAD(+)-dependent protein deacetylases 6 (SIRT6). A comparative study of the ABA-protein docked complex with already known inhibitors of these proteins relevant to diabetes was compared to explore the inhibitory potential. Calculation of molecular binding energy (ΔG), inhibition constant (pKi), and prediction of pharmacokinetics and pharmacodynamics properties were performed. The molecular docking investigation of ABA with 11-HSD1, GFAT, PPAR-gamma, and SIRT6 revealed considerably low binding energy (ΔG from −8.1 to −7.3 Kcal/mol) and predicted inhibition constant (pKi from 6.01 to 5.21 µM). The ADMET study revealed that ABA is a promising drug candidate without any hazardous effect following all current drug-likeness guidelines such as Lipinski, Ghose, Veber, Egan, and Muegge.     

Pregnane‐Type Steroidal Alkaloids of Sarcococca saligna: a New Class of Cholinesterase Inhibitors

Phytochemical investigation of Sarcococca saligna by extensive bioassay‐guided fractionation resulted in the isolation of the pregnane‐type steroidal alkaloids 1 – 15 , i.e. of the five new compounds 1 – 5 and the ten known alkaloids 6 – 15 . The structures of the new alkaloids salignenamide C ( 1 ), salignenamide D ( 2 ), 2β‐hydroxyepipachysamine D ( 3 ), salignenamide E ( 4 ), and salignenamide F ( 5 ) were elucidated with the help of modern spectroscopic techniques, while the known alkaloids axillarine C ( 6 ), axillarine F ( 7 ), sarcorine ( 8 ), N³‐demethylsaracodine ( 9 ), saligcinnamide ( 10 ), salignenamide A ( 11 ), vaganine A ( 12 ), axillaridine A ( 13 ), sarsalignone ( 14 ), and sarsalignenone ( 15 ) were identified by comparing their spectral data with those reported earlier. Inhibition of electric‐eel acetylcholinesterase (EC 3.1.1.7) and horse‐serum butyrylcholinesterase (EC 3.1.1.8) by alkaloids 1 – 15 were investigated. These new cholinesterase inhibitors may act as potential leads in the discovery of clinically useful inhibitors for nervous‐system disorders, particularly by reducing memory deficiency in Alzheimer's disease patients by potentiating and effecting the cholinergic transmission process. These compounds were found to inhibit both enzymes in a concentration‐dependent fashion with the IC₅₀ values ranging from 5.21–227.92 μM against acetylcholinesterase and 2.18–38.36 μM against butyrylcholinesterase.     

Correlation between Solution and the Solid State: The pH Dependent Composition in the Ternary System [Co(H2O)6]2+ or [Ni(H2O)6]2+/Piperazine/Phosphate

The protolytic equilibria of piperazine (C₄H₁₀N₂) and phosphate have been investigated in the presence of cobalt or nickel chloride or nitrate by potentiometric titrations between pH 2 and 8. Potentiometric titrations suggest the presence of [M²⁺(H₂O)₅(C₄H₁₁N₂⁺)]³⁺ and [M²⁺(H₂O)₅(C₄H₁₀N₂)]²⁺ in solution with stability constants logK of 3.1 and 3.8 for M = Co and 3.1 and 3.6 for M = Ni, respectively. Crystallization experiments were then conducted at selected pH values to isolate desired species from the known solution composition. Crystallization afforded [M(H₂O)₆]²⁺(C₄H₁₂N₂²⁺)(HPO₄^2—)₂ at pH 3.5 and 6.2 (M = Co, Ni), and Co₃(PO₄)₂·8H₂O at pH 10.5. No crystals with the dihydrogenphosphate anion or a metal‐bound piperazine ligand could be isolated under the reaction conditions. The solid‐state assembly in the isomorphous structures of [M(H₂O)₆](C₄H₁₂N₂)(HPO₄)₂ with M = Co and Ni is based on an extended hydrogen bonded network between the three ionic building blocks.     

Estimation of background radiation levels and associated health risks in mineral rich district Chiniot,Pakistan

The mineral extraction activities may disturb the natural radioactivity, therefore current study aims to generate baseline data of natural radionuclides and anthropogenic ¹³⁷Cs before the start of industrial activities. Gamma spectrometry and gross alpha and beta counting systems were used for activity measurement in environmental samples. In soil, the mean activity of ²³²Th, ²²⁶Ra, ⁴⁰K and ¹³⁷Cs were determined as 79 (66–117), 47 (34–80), 823 (602–1159) and 1.3 (1.1–4.5) Bq kg^?1, respectively. The average annual effective dose rate (128.7 µSv h^?1) in the study area was twice higher than world’s average value. Indoor hazard index was greater than unity at two places; therefore, proper ventilation is proposed during construction.

     

Hybrid cross‐linked hydrogels as a technology platform for in vitro release of cephradine

Hydrogel‐based drug delivery systems can leverage therapeutically favorable upshots of drug release and found clinical uses. Hydrogels offer temporal and spatial control over the release of different therapeutic agents. Because of their tailor made controllable degradability, physical properties, and ability to prevent the labile drugs from degradation, hydrogels provide platform on which diverse physicochemical interactions with entrapped drugs cause to control drug release. Herein, we report the fabrication of novel vinyltrimethoxy silane (VTMS) cross‐linked chitosan/polyvinyl pyrrolidone hydrogels. Swelling in distilled water in conjunction with different buffer and electrolyte solutions was performed to assess the swellability of hydrogels. Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), and X‐ray diffraction (XRD) analysis were further conducted to investigate the possible interactions between components, thermal stability, and crystallinity of as‐prepared hybrid hydrogels, respectively. In vitro time‐dependent biodegradability, antimicrobial study, and cytotoxicity were also carried out to evaluate their extensive biocompatibility and cytotoxic behavior. More interestingly, in vitro drug release study allowed for the controlled release of cephradine. Therefore, this facile strategy developed the novel biocompatible and biodegradable hybrid hydrogels, which could significantly expand the scope of these hydrogels in other biomedical applications like scaffolds, skin regeneration, tissue engineering, etc.     

Control of combined convection in a nanofluid-filled lid-driven closed space via rectangular bar in the presence of magnetic field

Journal of Thermal Analysis and Calorimetry - In the present study, a computational work has been done to see the heat transfer, fluid flow and temperature distribution in a lid-driven cavity due...     

Mixed convection and entropy production in a nanofluid-filled closed space with inclined magnetic field

Journal of Thermal Analysis and Calorimetry - A computational analysis has been performed to study the impact of magnetic field on entropy generation due to mixed convective nanofluid flow with top...     

Antioxidant, antimicrobial properties and phenolics of different solvent extracts from bark, leaves and seeds of Pongamia pinnata (L.) Pierre

This study appraises the antioxidant and antimicrobial attributes of various solvent extracts (absolute methanol, aqueous methanol, absolute ethanol, aqueous ethanol, absolute acetone, aqueous acetone, and deionized water) from bark, leaves and seeds of Pongamia pinnata (L.) Pierre. Maximum extraction yield of antioxidant components from bark (16.31%), leaves (11.42%) and seeds (21.51%) of P. pinnata was obtained using aqueous methanol (20:80). Of the extracts tested, the bark extract, obtained with aqueous methanol, exhibited greater levels of total phenolics [6.94 g GAE/100 g dry weight (DW)], total flavonoids (3.44 g CE/100 g DW), inhibition of linoleic acid peroxidation (69.23%) and DPPH radical scavenging activity (IC(50) value, 3.21 μg/mL), followed by leaves and seeds extracts. Bark extract tested against a set of bacterial and fungal strains also revealed the strongest antimicrobial activity with the largest inhibition zone and lowest minimum inhibitory concentration (MIC). HPLC analysis of aqueous methanol extracts from bark, leaves and seeds indicated the presence of protocatechuic, ellagic, ferulic, gallic, gentisic, 4-hydroxybenzoic and 4-hydroxycinnamic acids in bark (1.50-6.70 mg/100 g DW); sorbic, ferulic, gallic, salicylic and p-coumaric acids in leaves (1.18-4.71 mg/100 g DW); vanillic, gallic and tannic acids in seeds (0.52-0.65 mg/100 g DW) as the main phenolic acids. The present investigation concludes that the tested parts of P. pinnata, in particular the bark, have strong potential for the isolation of antioxidant and antimicrobial agents for functional food and pharmaceutical uses.     

Development and validation of HPLC method for simultaneous estimation of piperine and guggulsterones in compound Unani formulation (tablets) and a nanoreservoir system

An attempt has been made to develop and validate a simultaneous HPLC method for novel approach of drug release via oil‐in‐water (o/w) nanoemulsion formulation and Habb‐e‐Khardal Unani tablet containing piperine and guggul sterones E and Z as main ingredients. Nanoemulsion was prepared by titration method using sefsol‐218 as an oily phase, cremophor‐EL as a surfactant, transcutol as a co‐surfactant and distilled water as an aqueous phase. The formulation was optimized on the basis of thermodynamic stability and dispersibilty test. The nanoformulation was evaluated for particle size, surface morphology, electrical conductivity and viscosity determination. The in vitro dissolution was carried out by dialysis bag method. Drugs were quantified using an HPLC method developed in‐house with a C₁₈ column as stationary phase and acetonitrile and water as mobile phase at λ_max of 240 nm. The optimized formulation showed higher drug release, lower droplet size and less viscosity as compared with the conventional Habb‐e‐Khardal Unani tablet. The present study illustrated the potential of nanoemulsion dosage form in improving biopharmaceutic performance of piperine and guggul sterone. The HPLC method was also found to be quite sufficient for the routine quality control of formulations containing piperine and guggul sterone E and Z as ingredients and also for in vitro drug release studies. Copyright © 2011 John Wiley & Sons, Ltd.     

Copper perchlorate and tetrafluoridoborate compounds with the ligand 1,4,5-triazanaphthalene. Gradual transformation of mononuclear Cu(II) compounds via polynuclear mixed-valence Cu(II)/Cu(I) species to dinuclear Cu(I); syntheses, characterizations and X-ray structures

When the ligand 1,4,5-triazanaphthalene (abbreviated as tan) is reacted with Cu(II) BF(4)(-) and ClO(4)(-) salts, a variety of mononuclear compounds has been found, all with the [Cu(tan)(4)] unit and varying amounts of weakly coordinating axial ligands and lattice solvents. Reproducible compounds formed include two purple compounds, analyzing as [Cu(tan)(4)](ClO(4))(2)(CH(3)OH)(2)(H(2)O) (1) and [Cu(tan)(4)](BF(4))(2)(CH(3)OH)(1.5)(H(2)O) (3), and two blue compounds, analyzing as [Cu(tan)(4)](ClO(4))(2)(H(2)O)(2) (2) and [Cu(tan)(4)](2)(BF(4))(2)(H(2)O)(2) (4). Upon standing at room temperature, red-coloured, mixed-valence dinuclear-based 3D coordination polymers are formed by conversion of the purple/blue products, of which [Cu(2)(tan)(4)](n)(BF(4))(3n) (5) and the isomorphic methanol-water adduct [Cu(tan)(4)](n)(BF(4))(3n)(CH(3)OH)(n)(H(2)O)(5n) (5A) are presented in this paper. In addition a fully reduced dinuclear Cu(I) compound of formula [Cu(2)(tan)(3)(ClO(4))(2)] (7) has been observed, and structurally characterized, as a rare three-blade propeller structure, with a Cu-Cu distance of 2.504 ?.