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.     

First Higher‐Order Photocycloaddition to a CN Bond: 1,3‐Diazepines from Maleimides

A light touch is all that is required to cleave a maleimide C? N bond to effect a [5+2] photocycloaddition with a sterically encumbered C?N moiety (see scheme).

     

Dalitz plot analysis of the decay D(+)-->K(-)pi(+)pi(+) and indication of a low-mass scalar Kpi resonance

We study the Dalitz plot of the decay D(+)-->K(-)pi(+)pi(+) with a sample of 15090 events from Fermilab experiment E791. Modeling the decay amplitude as the coherent sum of known Kpi resonances and a uniform nonresonant term, we do not obtain an acceptable fit. If we allow the mass and width of the K(*)(0)(1430) to float, we obtain values consistent with those from PDG but the chi(2) per degree of freedom of the fit is still unsatisfactory. A good fit is found when we allow for the presence of an additional scalar resonance, with mass 797+/-19+/-43 MeV/c(2) and width 410+/-43+/-87 MeV/c(2). The mass and width of the K(*)(0)(1430) become 1459+/-7+/-5 MeV/c(2) and 175+/-12+/-12 MeV/c(2), respectively. Our results provide new information on the scalar sector in hadron spectroscopy.     

The effect of measurement on the quantum features of a chaotic system

We investigate the quantum dynamics of a periodically kicked nonlinear spin system which exhibits regular and chaotic dynamics in the classical regime. The quantum behaviour is characterised by the evolving eigenvalue distributions for the angular momentum components and the features, including recurrences in the quantum means and the presence of quantum tunneling, are discussed. We employ the evolution operator eigenvalue distribution to prove that coherent quantum tunneling occurs between the fixed points in the regular regions of phase space. Continual quantum measurement is included in the model: the classical dynamics are unchanged but a destruction of coherences occurs in the quantum system. Recurrences in the means are destroyed and quantum tunneling is suppressed by measurement, a manifestation of the quantum Zeno effect.