Department of Industrial Chemistry, Renaissance University, Ugbawka, Enugu State, Nigeria.
Department of Cardiovascular and Endocrine-Metabolic Diseases, and Aging, Italian National Institute of Health, Rome, Italy.
Expert Rev Clin Pharmacol. 2021 Apr;14(4):465-480. doi: 10.1080/17512433.2021.1901578. Epub 2021 Mar 30.
:Nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway plays a key role in diverse gene expressions responsible for protection against oxidative stress and xenobiotics. Chalcones with a common chemical scaffold of 1,3-diaryl-2- propen-1-one, are abundantly present in nature with a wide variety of pharmacological properties. This review will discuss the interactions of natural and synthetic chalcones with Nrf2 signaling.:Chalcones are reportedly found to activate Nrf2 signaling pathway, expression of Nrf2-regulated antioxidant genes, induce cytoprotective proteins and upregulate multidrug resistance-associated proteins. Chalcones being soft electrophiles are less prone to hostile off-target effects and unlikely to induce carcinogenicity and mutagenicity. Furthermore, their low toxicity, structural diversity, feasibility in structural reorganization and the presence of α,β-unsaturated carbonyl group which makes them suitable drug candidates targeting Nrf2-dependent diseases.:Nrf2-Keap1 signaling pathway plays a central role in redox signaling. However, available therapeutic agents for Nrf2 activation have limited practical applications due to their associated risks, relatively low efficacy and bioavailability. The designing and fabrication of new chemical entities with chalcone scaffold-based Michael acceptor mechanism should be aimed as potential therapeutic Nrf2 activators to target oxidative stress and inflammation-mediated diseases such as atherosclerosis, Parkinson's disease and many more.
:Nrf2 相关因子 2（Nrf2）信号通路在多种基因表达中起着关键作用，这些基因表达负责对抗氧化应激和外源性物质。查耳酮具有 1,3-二芳基-2-丙烯-1-酮的常见化学结构骨架，在自然界中大量存在，具有广泛的药理特性。本综述将讨论天然和合成查耳酮与 Nrf2 信号通路的相互作用。:查耳酮据报道能激活 Nrf2 信号通路，表达 Nrf2 调节的抗氧化基因，诱导细胞保护蛋白并上调多药耐药相关蛋白。查耳酮作为软亲电体，不易发生敌对的非靶标效应，不太可能引起致癌性和致突变性。此外，它们的低毒性、结构多样性、结构重排的可行性以及存在α,β-不饱和羰基，使它们成为针对 Nrf2 依赖性疾病的有前途的药物候选物。:Nrf2-Keap1 信号通路在氧化还原信号中起着核心作用。然而，由于其相关风险、相对低的疗效和生物利用度，用于 Nrf2 激活的现有治疗剂的实际应用受到限制。基于查耳酮骨架的迈克尔受体机制的新化学实体的设计和制造应作为潜在的治疗 Nrf2 激活剂，以针对氧化应激和炎症介导的疾病，如动脉粥样硬化、帕金森病等。
