染料木黄酮-O-烷基胺衍生物的合成及生物评价作为潜在的多功能抗阿尔茨海默病药物。
Synthesis and biological evaluation of genistein-O-alkylamine derivatives as potential multifunctional anti-Alzheimer agents.
机构信息
Huaihe Hospital, Henan University, Kaifeng, China.
Key Laboratory of Natural Medicine and Immuno-Engineering, Henan University, Kaifeng, China.
出版信息
Chem Biol Drug Des. 2019 Feb;93(2):188-200. doi: 10.1111/cbdd.13414. Epub 2018 Oct 21.
A series of genistein derivatives were synthesized and evaluated as multifunctional anti-Alzheimer agents. The results showed that these derivatives had significant acetylcholinesterase (AChE) inhibitory activity; compound 5a exhibited the strongest inhibition to AChE with an IC value (0.034 μM) much lower than that of rivastigmine (6.53 μM). A Lineweaver-Burk plot and molecular modeling study showed that compound 5a targeted both the catalytic active site and the peripheral anionic site of AChE. These compounds also showed potent peroxy scavenging activity and metal-chelating ability. The compounds did not show obvious effect on HepG2 and PC12 cell viability at the concentration of 100 μM. Therefore, these genistein derivatives can be utilized as multifunctional agents for the treatment of AD.
一系列染料木黄酮衍生物被合成并评估为多功能抗阿尔茨海默病药物。结果表明，这些衍生物具有显著的乙酰胆碱酯酶（AChE）抑制活性；化合物 5a 对 AChE 的抑制作用最强，IC 值（0.034 μM）远低于rivastigmine（6.53 μM）。Lineweaver-Burk 作图和分子模拟研究表明，化合物 5a 靶向 AChE 的催化活性位点和外周阴离子位点。这些化合物还表现出很强的过氧清除活性和金属螯合能力。在 100 μM 浓度下，这些化合物对 HepG2 和 PC12 细胞活力没有明显影响。因此，这些染料木黄酮衍生物可用作治疗 AD 的多功能药物。
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