In Silico Exploration of Potential Phytoconstituents from the Bark Extract of Boswellia serrata for Hemorrhoidal Disease: Molecular Docking and Molecular Dynamics Analysis.

Boswellia serrata Roxb. Ex Colebr is a popular medicinal plant used traditionally in herbal medicinal preparations to treat a variety of diseases. The purpose of the present investigation was to investigate the anti-hemorrhoidal property of the bark extract of B. serrata (BS). For this, the sequential Soxhlet extraction method was carried out by using different solvents such as hexane, chloroform, and methanol. After the extraction, the obtained dry extracts were tested for quantitative determinations such as total alkaloid content (TAC), total flavonoid content (TFC), total phenol content (TPC), and total tannin content (TTC) for all the extracts. Moreover, in vitro antioxidant activity was measured using 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging activity and scavenging activity against 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS). Methanolic bark extract showed the highest TPC (67.10±1.83), TFC (372.73±4.45), TAC (9.732±1.06), and TTC (48.932±1.82), as well as the antioxidant assays DPPH (IC50=9.88 µg/ml) and ABTS (IC50=15.09 µg/ml). In this study, both LC-MS and GC-MS were performed to identify the chemical composition of all the extracts. Consequently, 19 compounds were identified by GC-MS and 27 compounds were identified by LC-MS analysis. The identified phytoconstituent(s) that could potentially interact with the target protein cyclooxygenase-2 (COX-2) (PDB: 4RRW) using molecular dynamics simulation and in silico docking were studied. Three compounds that have passed in drug-likeness and ADME-Tox properties are having more docking score than the standard. In this study, camptothecin, justicidin B, and taxiphyllin are identified as potential lead compounds with anti-hemorrhoidal properties and may be helpful in the process of drug development and discovery of novel drugs. Hence, these results demonstrate that BS is a good source of pharmacologically active components with potential applications against hemorrhoidal disease.

2-{N-[(2,4,5-trichlorophenoxy) acetyl]-N-methylamino}-3-pyrrolidinepropanamide analogs as potential antagonists of Urotensin II receptor.

THE PURPOSE OF THE ARTICLE: To identify novel small molecule antagonists of Urotensin II receptor with acceptable pharmacological profile. MATERIALS AND METHODS: Structure-activity-relationship (SAR) studies on 2-{N-[(2,4,5-trichlorophenoxy) acetyl]-N-methylamino}-3-pyrrolidinepropanamide series were conducted and shortlisted compounds were synthesized and evaluated in in vitro cell-based assays. Human and mouse Urotensin II receptor overexpressing CHO cells were used for calcium release and radioligand binding assays. Initial molecules in this series had solubility and inter-species variability issue in the calcium release assay. We, therefore, conducted SAR to overcome these 2 issues and molecules with accepted in vitro profile were evaluated further in mouse pressor response model to generate the in vivo proof of concept for UII receptor antagonization. RESULTS AND CONCLUSIONS: We report herewith identification of 2-{N-[(2,4,5-trichlorophenoxy)acetyl]-N-methylamino}-3-pyrrolidinepropanamides series to obtain novel small molecule antagonists of Urotensin II receptor with acceptable pharmacological profile.

Compaction of RNA Duplexes in the Cell*.

The structure and flexibility of RNA depends sensitively on the microenvironment. Using pulsed electron-electron double-resonance (PELDOR)/double electron-electron resonance (DEER) spectroscopy combined with advanced labeling techniques, we show that the structure of double-stranded RNA (dsRNA) changes upon internalization into Xenopus laevis oocytes. Compared to dilute solution, the dsRNA A-helix is more compact in cells. We recapitulate this compaction in a densely crowded protein solution. Atomic-resolution molecular dynamics simulations of dsRNA semi-quantitatively capture the compaction, and identify non-specific electrostatic interactions between proteins and dsRNA as a possible driver of this effect.

Plasmon Mediated Single Photon Emission from a Nanocrystal Ensemble.

Quantum photonic devices require robust sources of single photons to perform basic computational and communication protocols. Thus, developing scalable, integrable, and efficient quantum light sources has become crucial for the realization of quantum photonic devices. Single quantum dots are promising sources of quantum light due to their tunable emission wavelength. Here, we show the emergence of quantum-emitter-like antibunched emission behavior when multiple quantum dots are located in the vicinity of plasmonic particles. To evaluate the robustness of this phenomenon, we consider both monometallic and bimetallic particles. We find that the photoluminescence intensity of the plasmon coupled quantum dots fits well to a single sublinear power law exponent that is distinct from the behavior of CQD aggregates. Significantly, we find that plasmon coupling results in reduced flickering, thus enabling the realization of a more stable and reliable single photon source. Possible roles of emergent excitonic interactions in the coupled system are discussed.

Physical Mechanisms of Improved Performance of Scaffolded Zinc-Silver Battery Cathodes.

Nanostructuring can greatly improve the electrode stability of rechargeable battery systems, such as Zn-Ag. In this report, we investigate the physical mechanisms by which nanostructuring alters structural properties of nanomaterials and thereby influences the structural stability of electrodes. We specifically consider the effects of Au-based nanoscaffolds on Ag. Through density functional theory calculations, we propose that the charge transfer at the Au-Ag interface can facilitate the formation of Ag2O from Ag centers. Structural analysis of samples prepared in this work shows that Ag2O is extruded from Au-Ag material in the form of sheets. Interestingly, the length scale of such protrusions depends on the Au mole fraction that significantly alters the system's overall structural morphology. We rationalize these findings via kinetic Monte Carlo simulations of the Ag2O growth process and highlight the role of Au as a heterogeneous nucleation center.

Enhancement of the electrochemical performance of zinc-silver batteries with a gold nano-scaffold.

Primary zinc-silver batteries are widely employed in military, aerospace, and marine applications. However, the development of secondary zinc-silver batteries is still a subject of on-going research. For example, these batteries suffer from rapid capacity loss during cycling due to instabilities of the zinc anode and the silver cathode. While there is a large body of work on the Zn anode, there is limited work toward stabilizing the Ag electrode and thereby achieving a long cycle life. In this work, we propose a gold-silver nanostructure where gold acts as a scaffolding material and improves the retention of structural integrity during cell cycling. We show that this nanostructure improves battery capacity as well as capacity retention after 35 cycles. Our work emphasizes the role of nanostructuring in enabling a newer secondary battery chemistry based on existing primary ones.

Simultaneous Localization of Two High Affinity Divalent Metal Ion Binding Sites in the Tetracycline RNA Aptamer with Mn2+-Based Pulsed Dipolar EPR Spectroscopy.

Mg2+ ions play an essential part in stabilizing the tertiary structure of nucleic acids. While the importance of these ions is well documented, their localization and elucidation of their role in the structure and dynamics of nucleic acids are often challenging. In this work, pulsed electron-electron double resonance spectroscopy (PELDOR, also known as DEER) was used to localize two high affinity divalent metal ion binding sites in the tetracycline RNA aptamer with high accuracy. For this purpose, the aptamer was labeled at different positions with a semirigid nitroxide spin label and diamagnetic Mg2+ was replaced with paramagnetic Mn2+, which did not alter the folding process or ligand binding. Out of the several divalent metal ion binding sites that are known from the crystal structure, two binding sites with high affinity were detected: one that is located at the ligand binding center and another at the J1/2 junction of the RNA.

Noncovalent spin-labeling of RNA: the aptamer approach.

In the first example of site-directed spin-labeling of unmodified RNA, a pyrrolidine-nitroxide derivative of tetramethylrosamine (TMR) was shown to bind with high affinity to the malachite green (MG) aptamer, as determined by continuous-wave (CW) electron paramagnetic resonance (EPR), pulsed electron-electron double resonance (PELDOR) and fluorescence spectroscopies.

Site-Directed Spin Labeling of RNA by Postsynthetic Modification of 2'-Amino Groups.

To elucidate mechanisms that govern functions of nucleic acids, it is essential to understand their structure and dynamics. Electron paramagnetic resonance (EPR) spectroscopy is a valuable technique that is routinely used to study those aspects of nucleic acids. A prerequisite for most EPR studies of nucleic acids is incorporation of spin labels at specific sites, known as site-directed spin labeling (SDSL). There are two main strategies for SDSL through formation of covalent bonds, i.e., the phosphoramidite approach and postsynthetic spin-labeling. After describing briefly the advantages and disadvantages of these two strategies, postsynthetic labeling of 2'-amino groups in RNA is delineated. Postsynthetic labeling of 2'-amino groups in RNA using 4-isocyanato-TEMPO has long been established as a useful approach. However, this method has some drawbacks, both with regard to the spin-labeling protocol and the flexibility of the spin label itself. Recently reported isothiocyanate-substituted aromatic isoindoline-derived nitroxides can be used to quantitatively and selectively modify 2'-amino groups in RNA and do not have the drawbacks associated with 4-isocyanato-TEMPO. This chapter provides a detailed description of the postsynthetic spin-labeling methods of 2'-amino groups in RNA with a special focus on using the aromatic isothiocyanate spin labels.

Site-directed spin labeling of 2'-amino groups in RNA with isoindoline nitroxides that are resistant to reduction.

Two aromatic isothiocyanates, derived from isoindoline nitroxides, were synthesized and selectively reacted with 2'-amino groups in RNA. The spin labels displayed limited mobility in RNA, making them promising candidates for distance measurements by pulsed EPR. After conjugation to RNA, a tetraethyl isoindoline derivative showed significant stability under reducing conditions.

TMIO-PyrImid hybrids are profluorescent, site-directed spin labels for nucleic acids.

We report the synthesis of a new class of molecules which are hybrids of long-lived tetramethylisoindolinoxyl (TMIO) radicals and the pyrido[1,2-a]benzimidazole (PyrImid) scaffold. These compounds represent a new lead for noncovalently binding nucleic acid probes, as they interact with nucleic acids with previously unreported C (DNA) and C/U (RNA) complementarity, which can be detected by electron paramagnetic resonance (EPR) techniques. They also have promising properties for fluorimetric analysis, as their fluorescent spin-quenched derivatives exhibit a significant Stokes shift.