设计、合成及二甲胺甲基取代姜黄素衍生物的抗阿尔茨海默病活性。
Design, synthesis and anti-Alzheimer properties of dimethylaminomethyl-substituted curcumin derivatives.
机构信息
Pharmaceutical Research Center and Jiangsu Province Hi-Tech Key Laboratory for Bio-medical Research, School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, China; State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
Pharmaceutical Research Center and Jiangsu Province Hi-Tech Key Laboratory for Bio-medical Research, School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, China.
出版信息
Bioorg Med Chem Lett. 2014 Jan 1;24(1):40-3. doi: 10.1016/j.bmcl.2013.12.011. Epub 2013 Dec 8.
Eight dimethylaminomethyl-substituted curcumin derivatives were designed and synthesized. The antioxidant test revealed that the synthesized compounds had higher free radical scavenging activity towards both 2,2-diphenyl-1-picrylhydrazyl free radicals (DPPH) (IC50 1.5-29.9μM) and galvinoxyl radicals (IC50 4.9-41.1μM) than the lead compound curcumin. Besides, compound 3a could effectively inhibit the Aβ self-aggregation in vitro. Investigated in phosphate-buffered solutions (pH=7.4) in the presence or absence of 0.1% FBS 3a showed a good stability while curcumin did not. Furthermore, 3a showed a good lipophilicity (logP=3.48), suggesting a potential ability to penetrate the blood-brain-barrier. The aqueous solubility of the hydrochloride salt of 3a (16.7mg/mL) has also been significantly improved as compared with curcumin (<0.1mg/mL).
设计并合成了 8 种二甲氨基甲基取代的姜黄素衍生物。抗氧化试验表明，与先导化合物姜黄素相比，合成的化合物对 2,2-二苯基-1-苦基肼自由基（DPPH）（IC50 为 1.5-29.9μM）和戊二醛自由基（IC50 为 4.9-41.1μM）具有更高的自由基清除活性。此外，化合物 3a 能够有效抑制 Aβ的体外自聚集。在磷酸盐缓冲溶液（pH=7.4）中进行研究，无论是否存在 0.1% FBS，3a 都表现出良好的稳定性，而姜黄素则没有。此外，3a 具有良好的亲脂性（logP=3.48），表明其具有穿透血脑屏障的潜力。与姜黄素（<0.1mg/mL）相比，3a 的盐酸盐（16.7mg/mL）的水溶性也得到了显著提高。
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