药学学报, 2019, 54(8): 1461-1469
引用本文:
高燕, 刘万冬, 阮班锋. 白藜芦醇-丁苯酞杂合物的合成及其神经保护活性[J]. 药学学报, 2019, 54(8): 1461-1469.
GAO Yan, LIU Wan-dong, RUAN Ban-feng. Synthesis and neuroprotective activity of resveratrol-3-n-butylphthalide hybrids[J]. Acta Pharmaceutica Sinica, 2019, 54(8): 1461-1469.

白藜芦醇-丁苯酞杂合物的合成及其神经保护活性
高燕1, 刘万冬2, 阮班锋1
1. 合肥工业大学食品与生物工程学院, 安徽 合肥 230009;
2. 安徽中医药大学药学院, 安徽 合肥 230012
摘要:
以邻羧基苯甲醛为起始化合物,通过硝化、还原和重氮化等反应得到6-溴丁苯酞,将其与取代苯乙烯偶联得到20个白藜芦醇-丁苯酞杂合物,其结构经1H NMR、13C NMR、ESI-MS确证。采用MTT法考察所有化合物对氧糖剥夺诱导大鼠脑皮层神经元损伤的体外保护活性;采用Western印迹考察目标化合物对大鼠脑皮层神经元保护的作用机制。结果显示,大多数化合物对大鼠脑皮层神经元具有较强的保护作用(动物实验经安徽中医药大学实验动物伦理委员会批准),其中化合物10h10i活性较为显著,其可能通过激活PI3K/Akt信号通路起到神经保护作用。
关键词:    白藜芦醇      丁苯酞      合成      神经保护      PI3K/Akt     
Synthesis and neuroprotective activity of resveratrol-3-n-butylphthalide hybrids
GAO Yan1, LIU Wan-dong2, RUAN Ban-feng1
1. School of Food and Biological Engineering, Hefei University of Technology, Hefei 230009, China;
2. College of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, China
Abstract:
6-Bromo-3-n-butylphthalide was obtained by nitration, reduction and diazotization from carboxybenzaldehyde. Twenty hybrids from substituted styrene and 6-bromo-3-n-butylphthalide were synthesized and the structure was confirmed by 1H NMR, 13C NMR and ESI-MS. All compounds were evaluated for neuroprotective activity against OGD/R-induced neurotoxicity in rat cortical neurons by MTT assay. The mechanism of neuroprotection was investigated by Western blot analyses. The results indicated that most of these compounds had a potent neuroprotective activity (All animal experiments were approved by the Experimental Animal Ethics Committee of Anhui University of Chinese Medicine), especially 10h and 10i showed significant effects, which may play a neuroprotective role by activating the PI3K/Akt signaling pathway.
Key words:    resveratrol    dl-3-n-butylphthalide    synthesis    neuroprotection    PI3K/Akt   
收稿日期: 2019-05-13
DOI: 10.16438/j.0513-4870.2019-0364
基金项目: 安徽省自然科学基金资助项目(1508085MB3).
通讯作者: 阮班锋,Tel/Fax:86-551-62901534,E-mail:ruanbf@hfut.edu.cn
Email: ruanbf@hfut.edu.cn
相关功能
PDF(529KB) Free
打印本文
0
作者相关文章
高燕  在本刊中的所有文章
刘万冬  在本刊中的所有文章
阮班锋  在本刊中的所有文章

参考文献:
[1] Ayuso MI, Gonzalo-Gobernado R, Montaner J. Neuroprotective diets for stroke[J]. Neurochem Int, 2017, 107:4-10.
[2] Sifat AE, Vaidya B, Abbruscato TJ. Blood-brain barrier protection as a therapeutic strategy for acute ischemic stroke[J]. AAPS J, 2017, 19:957-972.
[3] Vaidya B, Sifat AE, Karamyan VT, et al. The neuroprotective role of the brain opioid system in stroke injury[J]. Drug Discov Today, 2018, 23:1385-1395.
[4] Bastianetto S, Menard C, Quirion R. Neuroprotective action of resveratrol[J]. Biochim Biophys Acta, 2015, 1852:1195-1201.
[5] Chao J, Li H, Cheng KW, et al. Protective effects of pinostilbene, a resveratrol methylated derivative, against 6-hydroxydopamine-induced neurotoxicity in SH-SY5Y cells[J]. J Nutr Biochem, 2010, 21:482-489.
[6] Chang J, Rimando A, Pallas M, et al. Low-dose pterostilbene, but not resveratrol, is a potent neuromodulator in aging and Alzheimer's disease[J]. Neurobiol Aging, 2012, 33:2062-2071.
[7] Yin W, Lan L, Huang Z, et al. Discovery of a ring-opened derivative of 3-n-butylphthalide bearing NO/H2S-donating moieties as a potential anti-ischemic stroke agent[J]. Eur J Med Chem, 2016, 115:369-380.
[8] Barta-Szalai G, Borza I, Bozó E, et al. Oxamides as novel NR2B selective NMDA receptor antagonists[J]. Bioorg Med Chem Lett, 2004, 14:3953-3956.
[9] Wang X, Wang L, Li T, et al. Novel hybrids of optically active ring-opened 3-n-butylphthalide derivative and isosorbide as potential anti-ischemic stroke agents[J]. J Med Chem, 2013, 56:3078-3089.
[10] Wang W, Cha XX, Reiner J, et al. Synthesis and biological activity of n-butylphthalide derivatives[J]. Eur J Med Chem, 2010, 45:1941-1946.
[11] Sun B, Hoshino J, Jermihov K, et al. Design, synthesis, and biological evaluation of resveratrol analogues as aromatase and quinone reductase 2 inhibitors for chemoprevention of cancer[J]. Bioorg Med Chem, 2010, 18:5352-5366.
[12] Wang X, Wang L, Huang Z, et al. Synthesis and biological evaluation of nitric oxide releasing derivatives of 6-amino-3-nbutylphthalide as potential antiplatelet agents[J]. Bioorg Med Chem Lett, 2013, 23:1985-1988.
[13] Nobre SM, Muniz MN, Seferin M, et al. The synthesis of non-symmetrical stilbene analogs of trans-resveratrol using the same Pd catalyst in a sequential double-Heck arylation of ethylene[J]. Appl Org Chem, 2011, 25:289-293.
[14] Uzura S, Sekine-Suzuki E, Nakanishi I, et al. A facile and rapid access to resveratrol derivatives and their radioprotective activity[J]. Bioorg Med Chem Lett, 2016, 26:3886-3891.