Synergistic antinociceptive activity of combined aqueous extracts of <i>Artemisia campestris</i> and <i>Artemisia herba</i>-<i>alba</i> in several acute pain models

<p>In this study, total phenolic and flavonoid contents, acute toxicity and the antinociceptive activity of <i>Artemisia campestris</i> and <i>Artemisia herba</i>-<i>alba</i>, individually and in combination, were investigated using multiple forms of pain in animals. Our results have been shown that plants are relatively safe without clinical signs of toxicity in animals. Thus, extracts were presented high levels in phenolic and flavonoid contents. <i>Artemisia</i> decoctions with 100, 200, 400 mg/kg b-w studied dose, clearly attenuate chemical and thermal noxious stimuli in writhing, formalin and hot-plate tests, and significantly reduced paw oedema in formalin test. Additionally, binary combination forms exhibited a great improvement in intensity and amplitude of antinociceptive activity in comparison with both plants used individually by a relative interference with opioid system. Our findings suggested the central and peripheral analgesic properties and confirmed the folkloric medicinal use of these plants in pain symptom treatment.</p

Synthesis, in silico study, and biological evaluation of cyclosulfamide derivatives as new anticholinesterase inhibitors

International audienceAfter the great spread of Alzheimer's disease (AD) in the past few years, many researchers directed their work toward developing an effective treatment for this disease and to discovering very advanced drugs. Cyclosulfamides are considered as versatile pharmacophores in the construction of new molecules with excellent activities. Therefore, a series of cyclosulfamide have been synthesized and evaluated as anti-Alzheimer agents through in vitro acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibition. Most of tested compounds showed an average inhibitory activity against two targeted enzymes compared with the reference ligand. Specifically, 10a showed the best inhibition of AChE enzyme with an IC50=45.30±0.88µM; while 4a exhibited the most potent BuChE enzyme inhibition with an IC50=52.87±3.73µM. Further, we were able to determine a feasible binding mode for cyclosulfamide derivatives owing to molecular docking studies, which offered prospective evidence to identify significant interactions between the active site of AChE and the synthesized ligands. Following the encouraging findings of the molecular docking investigation, the complex AChE-10a was put through a 100ns Desmond of Schrodinger simulation of molecular dynamics (MD), during which the receptor-ligand combination showed significant stability after 10 ns of MD simulation