(20R,22R)-6α,7α-Epoxy-5α,27-dihydroxy-1-oxowitha-2,24-dienolide in Leaves of Withania somnifera: Isolation and its Crystal Structure

Abstract  (20R,22R)-6α,7α-Epoxy-5α,27-dihydroxy-1-oxowitha-2,24-dienolide (27-hydroxy-withanolide B) was isolated from Withania somnifera. The structure of the withanolide was established by spectral analysis and X-ray diffraction studies. The compound crystallizes in the orthorhombic space group P2₁2₁2₁ with unit cell parameters: a = 9.2163(3), b = 11.1828(4), c = 23.6146(9) ?, Z = 4. The crystal structure was refined to R = 0.0495 for 3,284 observed reflections. All the rings of the steroid skeleton are trans connected. Rings A and B exist in a half-chair conformation, ring C a chair, and five membered ring D is intermediate between a half-chair and an envelope. The δ-lactone ring E adopts a distorted sofa conformation. The twist along the length of the steroid nucleus is −6.5°. The characteristic pattern observed in the packing diagram is the appearance of twisted chains of molecules packed together to form layers. Index Abstract  Isolation and crystal structure analysis of (20R,22R)-6α,7α-epoxy-5α,27-dihydroxy-1-oxowitha-2,24-dienolide.      

In Silico Molecular Docking Analysis of Karanjin against Alzheimer’s and Parkinson’s Diseases as a Potential Natural Lead Molecule for New Drug Design,Development and Therapy

Parkinson’s disease (PD) and Alzheimer’s disease (AD) are neurodegenerative disorders that have emerged as among the serious health problems of the 21st century. The medications currently available to treat AD and PD have limited efficacy and are associated with side effects. Natural products are one of the most vital and conservative sources of medicines for treating neurological problems. Karanjin is a furanoflavonoid, isolated mainly from Pongamia pinnata with several medicinal plants, and has been reported for numerous health benefits. However, the effect of karanjin on AD and PD has not yet been systematically investigated. To evaluate the neuroprotective effect of karanjin, extensive in silico studies starting with molecular docking against five putative targets for AD and four targets for PD were conducted. The findings were compared with three standard drugs using Auto Dock 4.1 and Molegro Virtual Docker software. Additionally, the physiochemical properties (Lipinski rule of five), drug-likeness and parameters including absorption, distribution, metabolism, elimination and toxicity (ADMET) profiles of karanjin were also studied. The molecular dynamics (MD) simulations were performed with two selective karanjin docking complexes to analyze the dynamic behaviors and binding free energy at 100 ns time scale. In addition, frontier molecular orbitals (FMOs) and density-functional theory (DFT) were also investigated from computational quantum mechanism perspectives using the Avogadro-ORCA 1.2.0 platform. Karanjin complies with all five of Lipinski’s drug-likeness rules with suitable ADMET profiles for therapeutic use. The docking scores (kcal/mol) showed comparatively higher potency against AD and PD associated targets than currently used standard drugs. Overall, the potential binding affinity from molecular docking, static thermodynamics feature from MD-simulation and other multiparametric drug-ability profiles suggest that karanjin could be considered as a suitable therapeutic lead for AD and PD treatment. Furthermore, the present results were strongly correlated with the earlier study on karanjin in an Alzheimer’s animal model. However, necessary in vivo studies, clinical trials, bioavailability, permeability and safe dose administration, etc. must be required to use karanjin as a potential drug against AD and PD treatment, where the in silico results are more helpful to accelerate the drug development.     

Tirzepatide,a New Era of Dual-Targeted Treatment for Diabetes and Obesity: A Mini-Review

The prevalence of obesity and diabetes is an increasing global problem, especially in developed countries, and is referred to as the twin epidemics. As such, advanced treatment approaches are needed. Tirzepatide, known as a ‘twincretin’, is a ‘first-in-class’ and the only dual glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) receptor agonist, that can significantly reduce glycemic levels and improve insulin sensitivity, as well as reducing body weight by more than 20% and improving lipid metabolism. This novel anti-diabetic drug is a synthetic peptide analog of the human GIP hormone with a C₂₀ fatty-diacid portion attached which, via acylation technology, can bind to albumin in order to provide a dose of the drug, by means of subcutaneous injection, once a week, which is appropriate to its a half-life of about five days. Tirzepatide, developed by Eli Lilly, was approved, under the brand name Mounjaro, by the United States Food and Drug Administration in May 2022. This started the ‘twincretin’ era of enormously important and appealing dual therapeutic options for diabetes and obesity, as well as advanced management of closely related cardiometabolic settings, which constitute the leading cause of morbidity, disability, and mortality worldwide. Herein, we present the key characteristics of tirzepatide in terms of synthesis, structure, and activity, bearing in mind its advantages and shortcomings. Furthermore, we briefly trace the evolution of this kind of medical agent and discuss the development of clinical studies.     

Physical Interpretation of Mixed Ionic-electronic Conductive Polymer-coated Electrodes by a Simple Universal Impedance Model

A simple equivalent electrical circuit is used to obtain the physical parameters of electrical circuit elements from measured electrochemical impedance spectra. This model consists of four circuit elements with a clear physical meaning for each of the elements. Compared to complex models with multiple constant phase elements or Warburg impedances, our model is suitable for extracting physical values for important electrode parameters with low errors. The feasibility of the model was shown by investigating pure metal or polymer-coated electrodes. Here, gold electrodes were coated either with Poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT : PSS), Polypyrrole:poly(styrenesulfonate) (PPy : PSS), or (PEDOT/PPy) : PSS by means of electropolymerization. The model could demonstrate the ionic-electronic differences such as the ion accessibility of the differently coated electrodes. To prove the correctness of the model, the obtained results were compared to the literature.     

X-ray Structure Analysis of 4–[(3,3–Dimethyloxiranyl)–methoxy]-7H-furo[3,2-g][1]benzopyran-7-one

The title compound, C₁₆H₁₄O₅, a furanocoumarin crystallizes in the triclinic space group P1 . The unit cell parameters are a = 7.852(2), b = 8.485(1), c = 11.095(1) Å; α = 105.90(1), β = 103.18(2), γ = 95.07(1)°. The structure has been solved by direct methods. Final R = 0.048 for 1943 observed reflections. The furanocoumarin system is almost planar. The epoxide ring makes a dihedral angle with the fused ring system of 98.21(11)°. Molecules are held together by C—H… O hydrogen bonds.     

Polymerizable Solvent-free Organic Liquids: A New Approach for Large Area Flexible and Foldable Luminescent Films

The high demand for light-emitting and display devices made luminescent organic materials as attractive candidates. Solvent-free organic liquids are one of the promising emitters among them due to the salient features. However, the inherent limitations of forming sticky and noncurable surfaces must be addressed to become an alternate emitter for large-area device applications. Herein, we functionalized solvent-free organic liquids having monomeric emission in bulk with polymerizable groups to improve the processability. The polymerizable group on carbazole, naphthalene monoimide, and diketopyrrolopyrrole-based solvent-free liquid emitters enabled on-surface polymerization. These emitters alone and in combinations can be directly coated on a glass substrate without the help of solvents. Subsequent photo or thermal polymerization leads to stable, non-sticky, flexible, foldable, and free-standing large-area films with reasonably high quantum yield. Our demonstration of the tunable and white light-emitting films using polymerizable solvent-free liquids might be a potential candidate in flexible/foldable/stretchable electronics. The new concept of polymerizable liquid can be extended to other functional features suitable for futuristic applications.     

Crystal Structure of 5,7-Dimethoxy-8-(2-oxo-3-methylbutyl)-2 H-1-benzopyran-2-one (Isosibiricin)

The title compound, C₁₆H₁₈O₅, a simple coumarin crystallizes in the monoclinic space group P2₁/c with unit cell parameters a = 7.321(3), b = 21.111(9), c = 11.649(3) Å; β = 123.14(2)°. The structure has been solved by direct methods. The coumarin ring system is planar. The methoxy groups at C5 and C7 are almost coplanar with the coumarin mean plane. The crystal structure is stabilized by C–H… O hydrogen bonds.     

Crystal Structure of N-methyl Crotananinium Iodide — A Pyrrolizidine Alkaloid

The crystal structure of N-methyl crotananinium iodide has been determined by X-ray structure analysis. The compound crystallizes in the orthorhombic space group P2₁2₁2₁ with cell parameters a = 19.37(2), b = 7.70(2), c = 13.38(2) Å. The structure has been solved by Patterson and successive Fourier methods and refined by full matrix least-squares methods to an R-index of 0.075. The structural features of the title compound are noted and are compared with those of similar others of such pyrrolizidine alkaloids.     

Development of stability-indicating method for separation and characterization of benidipine forced degradation products using LC–MS/MS

The present study describes forced degradation of benidipine (BEN) as per  Q1A (R2) and Q1B guidelines of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use. BEN degraded under hydrolysis (neutral, acidic, and alkaline), hydrogen peroxide induced oxidation, and UV light mediated photolytic degradation. A total of 14 degradation products (DPs) were found in all degradation studies, comprising 4 hydrolytic DPs, 8 oxidative DPs, and 4 photolytic DPs. A selective stability-indicating method was developed using an XBridge BEH C18 column with gradient elution program consisting of ammonium acetate (10 mM, 4.8 pH, acetic acid) and acetonitrile. The flow rate was maintained at 1 ml min⁻¹. All DPs were separated well using the developed HPLC method and were characterized using LC–MS/MS data. As this method is effective in identifying and separating BEN and its DPs with sufficient resolution, it can be used in laboratories for quality control of drugs in daily routine analysis and stability studies.