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Millions of people worldwide are currently afflicted with neurologic conditions like a seizure, depression, stress, Alzheimer's disease, Parkinson's disease, and Huntington's disease. However, the precise etiopathology of these diseases is still unknown. Substantial studies are being conducted to discover more treatments against these disorders because many patients do not experience the therapeutic benefits that would be expected from using existing pharmaceutical strategies. Herbal medicines which have been used in traditional medicine for millennia to treat various neurological problems are also being investigated and scientifically assessed. Punicalagin is a known polyphenol that has significant antioxidant, anti-inflammatory, anti-viral, anti-proliferative, and anti-cancer properties. Around the world, traditional use of herbal drugs is gaining wider acceptance as a part of complementary and alternative medicine. The scientific community should pay attention to these many neuroprotective pharmacodynamic activities of Punicalagin to create effective pharmacotherapeutic plans, as evidenced by mounting data in pre-clinical research investigations. The current review describes the recent studies on the pharmacological effects of Punicalagin in a variety of neurological illnesses and paves the way for further study in this field. [ABSTRACT FROM AUTHOR]

In our present work, some novel substituted 4-phenyl-5-vinylpyrrolidin-2-one derivatives were designed, synthesized, and evaluated for their γ-aminobutyric acid-aminotransferase (GABA-AT) inhibition and in-vivo anticonvulsant activity. Among all the synthesized derivatives, compound 7f was observed as the most potent and competitive inhibitor of GABA-AT (IC50 = 46.29 ± 3.19 µM, Ki = 0.106 ± 0.004 μM). The in-vivo anticonvulsant activity against maximum electroshock (MES) and PTZ, induced seizures test of compound 7f, was observed very significantly (P < 0.05) in comparison with standard Vigabatrin and have shown an increase in the level of GABA in the cortex region of the brain. The ex-vivo studies have also suggested reduced tissue necrosis. Finally, In-silico molecular docking and dynamics studies of compound 7f have shown that it forms desired amino acid residue interactions with the GABA-AT and was stable for 50 ns in the active site pocket of the enzyme. [ABSTRACT FROM AUTHOR]

The cholinesterases are essential targets implicated in the pathogenesis of Alzheimer's disease (AD). In the present study, virtual screening and molecular docking are performed to identify the potential hits. Docking-post processing (DPP) and pose filtration protocols against AChE and BChE resulted in three hits (AW00308, HTS04089, and JFD03947). Molecular Mechanics-Generalized Born Surface Area (MM-GBSA) and molecular dynamics simulation analysis affirmed the stability and binding pattern of the docked complex JFD03947, which was further synthesized and evaluated for in vitro cholinesterase inhibition (AChE, IC50 = 0.062 µM; BChE, IC50 = 1.482 µM) activity. The enzyme kinetics study of the JFD03947 against hAChE and hBChE suggested a mixed type of inhibition. The results of thioflavin T-assay also elicited anti-Aβ aggregation activity by JFD03947. Further, biological evaluation of identified compound JFD03947 also showed neuroprotective ability against the SH-SY5Y neuroblastoma cell lines. [ABSTRACT FROM AUTHOR]

Some promising 4-thiazolone derivatives as lipoxygenase inhibitors were designed, synthesized, characterized and evaluated for anti-inflammatory activity and respective ulcerogenic liabilities. Compounds (1b, 1e, 3b, and 3e) exhibited considerable in vivo anti-inflammatory activity (57.61, 79.35, 75.00, and 79.35%) against carrageenan-induced rat paw edema model, whereas compounds (1e, 3b, and 3e) were found active against the arachidonic acid-induced paw edema model (55.38, 55.38, and 58.46%). The most potent compound (3e) exhibited lesser ulcerogenic liability compared to the standard diclofenac and zileuton. Further, the promising compounds (1e and 3e) were evaluated for in vitro lipoxygenase (LOX; IC50 = 12.98 µM and IC50 = 12.67 µM) and cyclooxygenase (COX) inhibition assay (COX-1; IC50 > 50 µM and, COX-2; IC50 > 50 µM). The enzyme kinetics of compound 3e was evaluated against LOX enzyme and supported by in silico molecular docking and molecular dynamics simulations studies. Overall, the results substantiated that 5-benzylidene-2-phenyl-4-thiazolones are promising pharmacophore for anti-inflammatory activity. [ABSTRACT FROM AUTHOR]

Novel Schiff bases of 1-(2-Aminoethyl)piperidine-3-carboxylic acid were synthesized, characterized and screened for anticonvulsant activity. Compounds were evaluated for in vitro blood-brain barrier (BBB) permeability by parallel artificial membrane permeability BBB assay (PAMPA-BBB). Compounds 5d, 5f, 5j, 5l, 5m, 5n, 5w, 5x and 5y elicited considerable in vitro permeability across BBB and further screened for in vivo anticonvulsant activity by sc-PTZ and DMCM-induced seizure models. The outcome of the in vivo models suggested that 5d, 5w, and 5y were most potent amongst the synthesized compounds. The neurotoxicity evaluation of 5d, 5w, and 5y by rotarod indicates no impairment of muscle coordination in comparison to standard diazepam. The MTT assay revealed that the test compounds (5d, 5w, and 5y) were not found to alter the cell viability considerably. In silico molecular docking and dynamics simulations were carried out on the homology modeled protein of human GABA transporter 1 (GAT1), which exhibited complementary interactions of compound 5w within the active binding pocket. [ABSTRACT FROM AUTHOR]