Identification of Novel Natural Product Inhibitors against Matrix Metalloproteinase 9 Using Quantum Mechanical Fragment Molecular Orbital-Based Virtual Screening Methods.

Matrix metalloproteinases (MMPs) are calcium-dependent zinc-containing endopeptidases involved in multiple cellular processes. Among the MMP isoforms, MMP-9 regulates cancer invasion, rheumatoid arthritis, and osteoarthritis by degrading extracellular matrix proteins present in the tumor microenvironment and cartilage and promoting angiogenesis. Here, we identified two potent natural product inhibitors of the non-catalytic hemopexin domain of MMP-9 using a novel quantum mechanical fragment molecular orbital (FMO)-based virtual screening workflow.

Chronic Hyperglycemia before Spinal Cord Injury Increases Inflammatory Reaction and Astrogliosis after Injury: Human and Rat Studies.

Traumatic spinal cord injury (SCI) can cause permanent disabilities that seriously reduce quality of life. We evaluated the effects of chronic hyperglycemia before SCI on inflammatory markers and functional recovery after SCI in human patients and a rat model. In the human study, multivariate logistical regression analysis revealed that hemoglobin A1c (HbA1c) values, reflecting average plasma glucose concentration over a 3 month period, at admission were a significant risk factor for poor functional recovery.

2-Furoic piperazide derivatives as promising drug candidates of type 2 diabetes and Alzheimer's diseases: In vitro and in silico studies.

The heterocyclic compounds have been extensively reported for their bioactivity potential. The current research work reports the synthesis of some new multi-functional derivatives of 2-furoic piperazide (1; 1-(2-furoyl)piperazine). The synthesis was initiated by reacting the starting compound 1 with 3,5-dichloro-2-hydroxybenzenesulfonyl chloride (2) in a basic, polar and protic medium to obtain the parent sulfonamide 3 which was then treated with different electrophiles, 4a-g, in a polar and aprotic medium to acquire the designed molecules, 5a-g.

Synthesis, enzyme inhibitory kinetics mechanism and computational study of -(4-methoxyphenethyl)--(substituted)-4-methylbenzenesulfonamides as novel therapeutic agents for Alzheimer's disease.

The present study comprises the synthesis of a new series of sulfonamides derived from 4-methoxyphenethylamine (). The synthesis was initiated by the reaction of with 4-methylbenzenesulfonyl chloride () in aqueous sodium carbonate solution at pH 9 to yield -(4-methoxyphenethyl)-4-methylbenzensulfonamide .This parent molecule was subsequently treated with various alkyl/aralkyl halides, (, using -dimethylformamide (DMF) as solvent and LiH as activator to produce a series of new -(4-methoxyphenethyl)--(substituted)-4-methylbenzenesulfonamides .

Molecular Docking and Dynamic Simulation of AZD3293 and Solanezumab Effects Against BACE1 to Treat Alzheimer's Disease.

The design of novel inhibitors to target BACE1 with reduced cytotoxicity effects is a promising approach to treat Alzheimer's disease (AD). Multiple clinical drugs and antibodies such as AZD3293 and Solanezumab are being tested to investigate their therapeutical potential against AD. The current study explores the binding pattern of AZD3293 and Solanezumab against their target proteins such as β-secretase (BACE1) and mid-region amyloid-beta (Aβ) (PDBIDs: 2ZHV & 4XXD), respectively using molecular docking and dynamic simulation (MD) approaches.

In Vitro, In Silico Elucidation of Antiurease Activity, Kinetic Mechanism and COX-2 Inhibitory Efficacy of Coagulansin A of Withania coagulans.

Urease enzyme plays a crucial role in the survival of Helicobacter pylori that contributes to different diseases, including peptic ulcer (gastric and duodenal ulcers). Coagulansin A is the steroidal lactone (withanolide) found in plants of solanaceae family such Withania coagulans. The current study was carried out to examine the in vitro urease, COX-2 inhibitory activity and effect on type II collagen expression of coagulansin A.

Kinetics and Molecular Docking Studies of 6-Formyl Umbelliferone Isolated from Angelica decursiva as an Inhibitor of Cholinesterase and BACE1.

Coumarins, which have low toxicity, are present in some natural foods, and are used in various herbal remedies, have attracted interest in recent years because of their potential medicinal properties. In this study, we report the isolation of two natural coumarins, namely umbelliferone () and 6-formyl umbelliferone (), from , and the synthesis of 8-formyl umbelliferone () from . We investigated the anti-Alzheimer disease (anti-AD) potential of these coumarins by assessing their ability to inhibit acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and β-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1).

Structural and sequence features of two residue turns in beta-hairpins.

Beta-turns in beta-hairpins have been implicated as important sites in protein folding. In particular, two residue β-turns, the most abundant connecting elements in beta-hairpins, have been a major target for engineering protein stability and folding. In this study, we attempted to investigate and update the structural and sequence properties of two residue turns in beta-hairpins with a large data set.

Immobilization of proteins onto poly(2-hydroxyethyl methacrylate) functionalized Fe-Au/core-shell nanoparticles via adsorption strategy.

Biocompatible magnetic nanocomposites of Fe-AuNPs and poly(2-hydroxylethyl methacrylate) (PHEMA) were employed as a strategic protein immobilization platform. The hybrid magnetic nanocomposites were prepared by applying a 'grafting to' ATRP protocol. Fe-AuNPs having Fe core and Au shell were initially prepared by the inverse micelle method.

Feeling of cold hands and feet is a highly heritable phenotype.

The prevalence of the feeling of cold hands and feet (FCHF) is high in the general population but the etiology of FCHF is largely unknown. The aim of the present study was to explore whether the FCHF is heritable. Eight hundred and ninety-four pairs of twins completed a question about FCHF.