The Key Laboratory of Major Autoimmune Diseases, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, The Key Laboratory of Anti-inflammatory and Immune Medicines, Ministry of Education, Hefei, 230032, China.
The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, China.
Chem Biol Interact. 2021 Jan 25;334:109350. doi: 10.1016/j.cbi.2020.109350. Epub 2020 Dec 8.
A series of 7-O-amide hesperetin derivatives were subjected to multi-target biological evaluation of anti-Alzheimer's disease. Most of the compounds showed good in vitro inhibitory activity against cholinesterase, of which compound 7c (7-O-(4-(morpholinoethyl)-acetamide) hesperetin) was the most effective anti-eqBuChE derivative (IC = 0.28 ± 0.05 μM) and exerted neuroprotective effects. Further biological evaluation found that compounds 4d, 4e and 7c showed strong antioxidant, anti-Aβ self-aggregation and anti-neuroinflammatory activities. Compound 7c could inhibit the expression of iNOS and COX-2 proteins and prevent LPS-induced inflammatory response in BV2 cells. In addition, compound 7c could chelate biometal ions such as Cu and Zn. In the vivo study, the MWM test confirmed that compound 7c could improve the cognitive impairment caused by scopolamine. In summary, the above studies have shown that the optimized compound 7c has great development potential as MTDL for the treatment of AD.
一系列 7-O-酰胺橙皮素衍生物进行了抗阿尔茨海默病的多靶点生物评价。大多数化合物对乙酰胆碱酯酶表现出良好的体外抑制活性，其中化合物 7c（7-O-（4-（吗啉乙基）-乙酰胺）橙皮素）是最有效的抗 eqBuChE 衍生物（IC = 0.28 ± 0.05 μM），并具有神经保护作用。进一步的生物学评价发现，化合物 4d、4e 和 7c 表现出较强的抗氧化、抗 Aβ 自聚集和抗神经炎症活性。化合物 7c 可抑制 iNOS 和 COX-2 蛋白的表达，并可预防 LPS 诱导的 BV2 细胞炎症反应。此外，化合物 7c 可以螯合生物金属离子，如 Cu 和 Zn。在体内研究中，MWM 测试证实，化合物 7c 可改善东莨菪碱引起的认知障碍。综上所述，上述研究表明，优化后的化合物 7c 作为治疗 AD 的多靶治疗药物具有很大的发展潜力。
