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1.
Neurochem Int ; 178: 105799, 2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-38950625

RESUMO

Alumunium usage and toxicity has been a global concern especially an increased use of nanoparticulated aluminum (Al-NPs) products from the environment and the workplace. Al degrades in to nanoparticulate form in the environment due to the routine process of bioremediation in human body. Al-NPs toxicity plays key role in the pathophysiology of neurodegeneration which is characterised by the development of neurofibrillary tangles and neuritic plaques which correlates to the Alzheimer's disease. This study evaluated the Al-NPs induced neurodegeneration and causative behavioral alterations due to oxidative stress, inflammation, DNA damage, ß-amyloid aggregation, and histopathological changes in mice. Furthermore, the preventive effect of naringenin (NAR) as a potent neuroprotective flavonoid against Al-NPs induced neurodegeneration was assessed. Al-NPs were synthesized and examined using FTIR, XRD, TEM, and particle size analyzer. Mice were orally administered with Al-NPs (6 mg/kg b.w.) followed by NAR treatment (10 mg/kg b.w. per day) for 66 days. The spatial working memory was determined by novel object recognition, T-maze, Y-maze, and Morris Water Maze tests. We measured nitric oxide, advanced oxidation of protein products, protein carbonylation, lipid peroxidation, superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, reduced glutathione, oxidised glutathione, and acetylcholine esterase, as well as cytokines analysis, immunohistochemistry, and DNA damage. Al-NPs significantly reduced the learning memory power, increased oxidative stress, reduced antioxidant enzymatic activity, increased DNA damage, altered the levels of cytokines, and increased ß-amyloid aggregation in the cortex and hippocampus regions of the mice brain. These neurobehavioral impairments, neuronal oxidative stress, and histopathological alterations were significantly attenuated by NAR supplementation. In conclusion, Al-NPs may be potent neurotoxic upon exposure and that NAR could serve as a potential preventive measure in the treatment and management of neuronal degeneration.

2.
J Org Chem ; 88(24): 16829-16844, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38038383

RESUMO

A green approach for the synthesis of electrophilic alkenes has been developed via Knoevenagel condensation between active methylene compounds and carbonyl compounds using Mg powder under aqueous conditions. In this strategy, Mg(OH)2 acts as a catalyst, which was generated in situ by the reaction between metallic Mg (20 mol %) and water. Mg was found to be an efficient, nontoxic, and inexpensive metal catalyst system for producing a range of electrophilic alkenes in excellent yields (≤98%). A gram-scale synthesis of electrophilic alkenes has been developed, and Mg metal was recovered and recycled up to three times without an appreciable loss of catalytic activity. A catalytic cycle was proposed, and the reaction mechanism was investigated using density functional theory. The key steps are enolization of ethyl cyanoacetate, C-C bond formation, and then regeneration of the catalyst via metathesis with H2O. The overall reaction occurs easily with a maximum ΔG°â§§ value of 7.9 kcal/mol for the rate-determining C-C bond formation step. Our protocol has several advantages and can be further extended to one-pot sequential Knoevenagel condensation and Michael addition, and one-pot sequential Knoevenagel condensation and chemoselective reduction can be used for the synthesis of valuable precursors of pharmaceutical products under green and aqueous conditions.

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