Puksasook Thanchanok, Kimura Shinya, Tadtong Sarin, Jiaranaikulwanitch Jutamas, Pratuangdejkul Jaturong, Kitphati Worawan, Suwanborirux Khanit, Saito Naoki, Nukoolkarn Veena
Department of Pharmacognosy, Faculty of Pharmacy, Mahidol University, Bangkok, 10400, Thailand.
Graduate School of Pharmaceutical Sciences, Meiji Pharmaceutical University, Tokyo, 204-8588, Japan.
J Nat Med. 2017 Oct;71(4):665-682. doi: 10.1007/s11418-017-1097-2. Epub 2017 Jun 9.
A series of prenylated resveratrol derivatives were designed, semisynthesized and biologically evaluated for inhibition of β-secretase (BACE1) and amyloid-β (Aβ) aggregation as well as free radical scavenging and neuroprotective and neuritogenic activities, as potential novel multifunctional agents against Alzheimer's disease (AD). The results showed that compound 4b exhibited good anti-Aβ aggregation (IC = 4.78 µM) and antioxidant activity (IC = 41.22 µM) and moderate anti-BACE1 inhibitory activity (23.70% at 50 µM), and could be a lead compound. Moreover, this compound showed no neurotoxicity along with a greater ability to inhibit oxidative stress on P19-derived neuronal cells (50.59% cell viability at 1 nM). The neuritogenic activity presented more branching numbers (9.33) and longer neurites (109.74 µm) than the control, and was comparable to the quercetin positive control. Taken together, these results suggest compound 4b had the greatest multifunctional activities and might be a very promising lead compound for the further development of drugs for AD.
设计、半合成了一系列异戊烯基白藜芦醇衍生物，并对其抑制β-分泌酶（BACE1）和淀粉样β蛋白（Aβ）聚集以及清除自由基、神经保护和促神经突生长活性进行了生物学评估，以作为抗阿尔茨海默病（AD）的潜在新型多功能药物。结果表明，化合物4b表现出良好的抗Aβ聚集活性（IC = 4.78 μM）和抗氧化活性（IC = 41.22 μM）以及中等的抗BACE1抑制活性（50 μM时为23.70%），可能是一种先导化合物。此外，该化合物对源自P19的神经元细胞无神经毒性，且具有更强的抑制氧化应激能力（1 nM时细胞活力为50.59%）。与对照组相比，其促神经突生长活性表现为更多的分支数（9.33）和更长的神经突（109.74 μm），与槲皮素阳性对照相当。综上所述，这些结果表明化合物4b具有最强的多功能活性，可能是一种非常有前景的先导化合物，用于进一步开发AD药物。
