Emetine and Indirubin- 3- monoxime interaction with human brain acetylcholinesterase: A computational and statistical analysis

Alzheimer's disease is a chronic neurodegenerative ailment and the most familiar type of dementia in the older population with no effective cure to date. It is characterized by a decrease in memory, associated with the mutilation of cholinergic neurotransmission. Presently, acetylcholinesterase inhibitors have emerged as the most endorsed pharmacological medications for the symptomatic treatment of mild to moderate Alzheimer's disease. This study aimed to research the molecular enzymatic inhibition of human brain acetylcholinesterase by a natural compound emetine and I3M. Molecular docking studies were used to identify superior interaction between enzyme acetylcholinesterase and ligands. Furthermore, the docked acetylcholinesterase-emetine complex was validated statistically using an analysis of variance in all tested conformers. In this interaction, H-bond, hydrophobic interaction, pi-pi, and Cation-pi interactions played a vital function in predicting the accurate conformation of the ligand that binds with the active site of acetylcholinesterase. The conformer with the lowest free energy of binding was further analyzed. The binding energy for acetylcholinesterase complex with emetine and I3M was -9.72kcal/mol and -7.09kcal/mol, respectively. In the current study, the prediction was studied to establish a relationship between binding energy and intermolecular energy (coefficient of determination [R2 linear = 0.999), and intermolecular energy and Van der wall forces (R2 linear = 0.994). These results would be useful in gaining structural insight for designing novel lead compounds against acetylcholinesterase for the effective management of Alzheimer's disease.

New Approach in the Application of Conjugated Polymers: The Light-Activated Source of Versatile Singlet Oxygen Molecule

For many years, the research on conjugated polymers (CPs) has been mainly focused on their application in organic electronics. Recent works, however, show that due to the unique optical and photophysical properties of CPs, such as high absorption in UV–Vis or even near-infrared (NIR) region and efficient intra-/intermolecular energy transfer, which can be relatively easily optimized, CPs can be considered as an effective light-activated source of versatile and highly reactive singlet oxygen for medical or catalytic use. The aim of this short review is to present the novel possibilities that lie dormant in those exceptional polymers with the extended system of π-conjugated bonds.

The study of intramolecular decay and intermolecular energy transfer for phosphorescent organic light-emitting devices

Compared to the PtOO7-based system, the greater EQE of the PtON7-based system is mainly governed by the stronger energy transfer efficiency (ηEET); thus, it is necessary to evaluate ηEET from hosts to guests for the rational design of OLEDs.

Mapping the cooperativity pathways in spin crossover complexes

The abruptness of spin crossover (SCO) is related to intermolecular energy changes occurring over the course of an SCO transition. Crossover is abrupt when SCO-induced strain is accommodated synergistically in a few key interactions.

Hirshfeld Surface Analysis and Energy Framework for Crystals of Quinazoline Methylidene Bridged Compounds

The crystal structures of 4-(3,4-dimethoxyphenylethylamino)-methylidene-2,3,4,10-tetrahydro-1H-pyrido[2,1-b]-quinazolin-10-one (1) and 4-(3,4-methylene-dioxyphenylethylamino)-methylidene-2,3,4,10-tetrahydro-1H-pyrido[2,1-b]-quina-zolin-10-one hydrochloride (2) were studied by single crystal X-ray diffraction. Their molecular and crystal structures are described in the context of intra- and inter-molecular interactions and of stereoisomerism. The crystallographic study established mixed E, Z configuration about the C4=C12 bond for (1) and E configuration about the C4=C12 bond for (2). For molecular crystals, Hirshfeld surface analyses may provide insight into intermolecular interactions, and energy framework analyses allow one to quantify different contributions to the overall energy. These analyses were performed to pinpoint intermolecular interactions in (1) and (2). According to our results, the molecules are associated with intra- and intermolecular hydrogen bonds, C-H···π and π-stacking interactions. The three-dimensional Hirshfeld surface analyses and two-dimensional fingerprint plots revealed that the structures are dominated by H···H, H···C/C···H and H···O/O···H contacts. The intermolecular energy analysis confirmed a significant contribution of dispersion to the stabilization of molecular packings in (1) and (2).

LEAD MOLECULE IDENTIFICATION FROM VITEX TRIFOLIA LINN FOR HELMINTHIASIS USING IN VITRO AND IN SILICO METHODS

Objective: The study was an attempt to discover a lead molecule to treat helminthiasis using Vitex trifolia. Linn (V. folia Linn) through sterile effect, in vitro and in silico evaluation. Methods: The antibacterial activity was done by Kirby-Bauer disc diffusion method in three different concentrations of extract and in vitro anthelmintic activity was carried out by petri dish and organ bath method. Further, the in silico docking studies were carried out by 11 phytoconstituents against phosphoethanolamine methyltransferase (4FGZ) using Auto Dock 4.2, it was working based on the principle of Lamarckian genetic algorithm. In docking studies, three important parameters such as binding energy, inhibition constant and intermolecular energy are determined. Results: The extracts showed an antibacterial effect in three different concentrations. At 16 mcg/disc a significant effect was observed when compared to blank and ciprofloxacin 5 mcg/disc. The anthelmintic activity in the petri dish method, means paralyzing time of Pheretimaposthuma with the dose of 25, 50 and 100 mg/ml were 13.78, 5.79 and 4.57 min respectively and Piperazine citrate (10 mg/ml) showed paralysis in 21.58 min. In the organ bath method, the time for paralysis of the worm was recorded on a slow-moving Sherrington rotating drum and the study report showed that paralyzing time was decreased at increasing concentrations of the extract. The results of in silico studies exhibited a binding energy of-10.25kcal/mol, inhibitory constant (Ki) 30.91nM, intermolecular energy,-10.84kcal/mol for abietatriene-3-ol which is lesser than the standard ligand phosphoethanolamine (-6.03kcal/mol, 38.29µM,-7.82kcal/mol) respectively. Conclusion: The study reports conclude that the active constituents in V. folia Linn having better anthelmintic activity, thus the active constituents may be optimized and make way to a new moiety for the treatment of helminthiasis.