Anti-Inflammatory and Anti-Rheumatic Potential of Selective Plant Compounds by Targeting TLR-4/AP-1 Signaling: A Comprehensive Molecular Docking and Simulation Approaches

Plants are an important source of drug development and numerous plant derived molecules have been used in clinical practice for the ailment of various diseases. The Toll-like receptor-4 (TLR-4) signaling pathway plays a crucial role in inflammation including rheumatoid arthritis. The TLR-4 binds with pro-inflammatory ligands such as lipopolysaccharide (LPS) to induce the downstream signaling mechanism such as nuclear factor κappa B (NF-κB) and mitogen activated protein kinases (MAPKs). This signaling activation leads to the onset of various diseases including inflammation. In the present study, 22 natural compounds were studied against TLR-4/AP-1 signaling, which is implicated in the inflammatory process using a computational approach. These compounds belong to various classes such as methylxanthine, sesquiterpene lactone, alkaloid, flavone glycosides, lignan, phenolic acid, etc. The compounds exhibited different binding affinities with the TLR-4, JNK, NF-κB, and AP-1 protein due to the formation of multiple hydrophilic and hydrophobic interactions. With TLR-4, rutin had the highest binding energy (−10.4 kcal/mol), poncirin had the highest binding energy (−9.4 kcal/mol) with NF-κB and JNK (−9.5 kcal/mol), respectively, and icariin had the highest binding affinity (−9.1 kcal/mol) with the AP-1 protein. The root means square deviation (RMSD), root mean square fraction (RMSF), and radius of gyration (RoG) for 150 ns were calculated using molecular dynamic simulation (MD simulation) based on rutin’s greatest binding energy with TLR-4. The RMSD, RMSF, and RoG were all within acceptable limits in the MD simulation, and the complex remained stable for 150 ns. Furthermore, these compounds were assessed for the potential toxic effect on various organs such as the liver, heart, genotoxicity, and oral maximum toxic dose. Moreover, the blood–brain barrier permeability and intestinal absorption were also predicted using SwissADME software (Lausanne, Switzerland). These compounds exhibited promising physico-chemical as well as drug-likeness properties. Consequently, these selected compounds portray promising anti-inflammatory and drug-likeness properties.     

Reactions of 4-nitro-1,2,3-triazole with alkylating agents and compounds with activated multiple bonds

When 4-nitro-1,2,3-triazole is alkylated, a mixture of N₁- and N₂-isomers is formed, with the latter usually predominating. The same behavior is also observed in addition reactions of 4-nitrotriazole to activated multiple bonds.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 932–935, July, 1986.     

Synthesis and properties of vinyl ethers of 3,4-di(hydroxymethyl)-1,2,5-oxadiazole

The direct vinylation of 3,4-di(hydroxymethyl)-1,2,5-oxadiazole by acetylene was accomplished for the first time; its mono- and divinyl ethers were synthesized in the presence of cadmium acetate. The physicochemical and spectral properties and conformational structure of the synthesized compounds were studied. It was shown that the s-trans-trans-conformation is the most profitable for the divinyl ether of 3,4-di(hydroxymethyl)-1,2,5-oxadiazole.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1044–1047, August, 1984.     

Discrete expansions of continuum wave functions

Different methods of expanding continuum wave functions in terms of discrete basis sets are discussed. The convergence properties of these expansions are investigated, both from a mathematical and a numerical point of view, for the case of potentials of Woods-Saxon and square well type.     

Experimental Validation of Linear-Stability Theory Applied to a Submerged Jet

Doklady Physics - A submerged air jet of circular cross section of 0.12 m in diameter and a long laminar region (~5 jet diameters) is obtained experimentally at the Reynolds number of 5400. Within...     

Few-bubble luminescence in the acoustic field of a spherical resonator in aqueous solutions of sodium and terbium compounds

Stabilization and the luminescence mode during slight motion around the equilibrium position of a few (two to eight) bubbles in 2–6 mol/L aqueous solutions of NaCl, NaOH, TbCl saturated with argon were achieved in a device for monitoring single-bubble sonoluminescence in a spherical resonator. Examples are presented of this variety of multibubble sonoluminescence illustrating various spatial-spectral distributions of cavitation bubbles, which contain either emitters comprising only the solvent continuum or also metal emitters (Na*, Tb³⁺*). Stabilization of bubbles in the form of closely (0.5–1 mm) located pairs of bubbles is of particular interest, in one of which only the solvent luminesces, and in the other, a metal.