Oxidative stress and carbonyl stress resulting from the toxicity of small aldehydes are part of the detrimental mechanisms leading to neuronal cell loss involved in the progression of neurodegenerative diseases such as Alzheimer's disease. Polyunsaturated alkylated lipophenols represent a new class of hybrid molecules that combine the health benefits of anti-inflammatory omega-3 fatty acids with the anti-carbonyl and oxidative stress (anti-COS) properties of (poly)phenols in a single pharmacological entity. To investigate the therapeutic potential of quercetin-3-docosahexaenoic acid-7-isopropyl lipophenol in neurodegenerative diseases, three synthetic pathways using chemical or chemo-enzymatic strategies were developed to access milligram or gram scale quantities of this alkyl lipophenol. The protective effect of quercetin-3-DHA-7-iPr against cytotoxic concentrations of acrolein (a carbonyl stressor) was assessed in human SHSY-5Y neuroblastoma cells to underscore its ability to alleviate harmful mechanisms associated with carbonyl stress in the context of neurodegenerative diseases.

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烷基槲皮素脂酚合成及其对神经变性中羰基应激的保护作用概述

由小醛的毒性引起的氧化应激和羰基应激是导致神经元细胞损失的有害机制的一部分，该损失参与神经退行性疾病（例如阿尔茨海默病）的进展。多不饱和烷基化脂酚代表了一类新型混合分子，它将抗炎 omega-3 脂肪酸的健康益处与（聚）酚的抗羰基和氧化应激（抗 COS）特性结合在单一药理实体中。为了研究槲皮素-3-二十二碳六烯酸-7-异丙基脂酚在神经退行性疾病中的治疗潜力，开发了三种使用化学或化学酶策略的合成途径来获得毫克或克级数量的这种烷基脂酚。在人 SHSY-5Y 神经母细胞瘤细胞中评估了槲皮素-3-DHA-7- i Pr 对细胞毒性浓度的丙烯醛（一种羰基应激源）的保护作用，以强调其在神经退行性病变背景下减轻与羰基应激相关的有害机制的能力疾病。