Citation: Wu Jianbing, Yin Wei, Zhang Yinqiu, Ye Hui, Li Yunman, Tian Jide, Huang Zhangjian, Zhang Yihua. Design and synthesis of the ring-opened derivative of 3-n-butylphthalide-ferulic acid-glucose trihybrids as potential anti-ischemic agents[J]. Chinese Chemical Letters, ;2020, 31(7): 1881-1886. doi: 10.1016/j.cclet.2020.02.031 shu

Design and synthesis of the ring-opened derivative of 3-n-butylphthalide-ferulic acid-glucose trihybrids as potential anti-ischemic agents

Wu Jianbing ^a ,
Yin Wei ^a ,
Zhang Yinqiu ^a ,
Ye Hui ^a ,
Li Yunman ^b,*, ,
Tian Jide ^c ,
Huang Zhangjian ^a,*, ,
Zhang Yihua ^a,*,

a.
State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Drug Discovery, China Pharmaceutical University, Nanjing 210009, China
b.
State Key Laboratory of Natural Medicines, Department of Physiology, China Pharmaceutical University, Nanjing 210009, China
c.
Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA 90095, United States

liyunman@cpu.edu.cn

zhangjianhuang@cpu.edu.cn

zyhtgd@163.com

Received Date: 22 December 2019
Revised Date: 15 February 2020
Accepted Date: 17 February 2020
Available Online: 18 February 2020

Figures(5)

To improve aqueous solubility and anti-ischemic activity of 3-n-butylphthalide (NBP), we designed and synthesized the ring-opened derivative of NBP-ferulic acid-glucose trihybrids (S1-S8). These hybrids inhibited adenosine diphosphate (ADP)- or arachidonic acid (AA)-induced platelet aggregation, among them, S2 was 30-fold more water-soluble, and over 10-fold more potent in inhibition of platelet aggregation, as well as reduced ROS generation and protected primary neuronal cells from OGD/Rinduced damage, in comparison with NBP. Additionally, S2 was more active than its three moieties alone or in combination, suggesting that the activity of S2 may be attributed to the synergistic effects of these moieties. Importantly, in vivo studies indicated that S2 not only possessed good pharmacokinetic profile, but also improved NBP distribution in rodent brain, suggesting that the glucose moiety in S2 may be recognized by glucose transporter 1 (GLUT1) on blood-brain barrier (BBB), promoting it to penetrate through BBB. Our findings suggest that S2 may be a promising candidate for the intervention of ischemic stroke, warranting further study.
- 3-n-Butylphthalide,
- Ferulic acid,
- Glucose,
- Hybrids,
- Ischemic,
- Brain-blood barrier
1. [1]
  V.L. Feigin, M.H. Forouzanfar, R. Krishnamurthi, et al., Lancet 383 (2014) 245-254. doi: 10.1016/S0140-6736(13)61953-4
2. [2]
  C.J. Sommer, Acta Neuropathol. 133 (2017) 245-261. doi: 10.1007/s00401-017-1667-0
3. [3]
  Q.W. Zhang, L. Jiang, G. Wang, J.Q. Li, Chin. Chem. Lett. 28 (2017) 1505-1508. doi: 10.1016/j.cclet.2017.02.003
4. [4]
  X. Zhu, X. Li, J. Liu, Eur. J. Pharmacol. 500 (2004) 221-230. doi: 10.1016/j.ejphar.2004.07.027
5. [5]
  C. Qin, P. Zhou, L. Wang, et al., J. Cereb. Blood Flow Metab. 39 (2018) 2011-2021.
6. [6]
  J. Jia, C. Wei, J. Liang, et al., Alzheimer's Dementia 12 (2016) 89-99. doi: 10.1016/j.jalz.2015.04.010
7. [7]
  Y. Zhu, S. Tan, China J. Pract. Nerv. Dis. 13 (2010) 10-12.
8. [8]
  X. Wang, Y. Li, Q. Zhao, et al., Org. Biomol. Chem. 9 (2011) 5670-5681. doi: 10.1039/c1ob05478c
9. [9]
  J. Li, S. Xu, Y. Peng, et al., Acta Pharmacol. Sin. 39 (2018) 275-285. doi: 10.1038/aps.2017.90
10. [10]
  X. Sheng, K. Hua, C. Yang, et al., Bioorg. Med. Chem. Lett. 25 (2015) 3535-3540. doi: 10.1016/j.bmcl.2015.06.090
11. [11]
  X. Wang, L. Wang, T. Li, et al., J. Med. Chem. 56 (2013) 3078-3089. doi: 10.1021/jm4001693
12. [12]
  Y. Wang, Y. Huang, Y. Xu, et al., Antioxid. Redox Signal. 28 (2018) 141-163. doi: 10.1089/ars.2017.7003
13. [13]
  X. Wang, L. Wang, Z. Huang, et al., Bioorg. Med. Chem. Lett. 23 (2013) 1985-1988. doi: 10.1016/j.bmcl.2013.02.035
14. [14]
  A. Chamorro, U. Dirnagl, X. Urra, A.M. Planas, Lancet Neurol.15 (2016) 869-881. doi: 10.1016/S1474-4422(16)00114-9
15. [15]
  R. Rodrigo, R. Fernandez-Gajardo, R. Gutierrez, et al., CNS Neurol. Disord. Drug Targets 12 (2013) 698-714.
16. [16]
  C. Cheng, T. Ho, E. Lee, et al., Am. J. Chin. Med. 36 (2008) 1105-1119. doi: 10.1142/S0192415X08006570
17. [17]
  J. Li, Y. Zhao, G. Zhong, et al., Acta Pharm. Sin. 46 (2011) 305-310.
18. [18]
  Z. Ren, R. Zhang, Y. Li, et al., Int. J. Mol. Med. 40 (2017) 1444-1456. doi: 10.3892/ijmm.2017.3127
19. [19]
  W.M. Pardridge, Physiol. Rev. 63 (1983) 1481-1535. doi: 10.1152/physrev.1983.63.4.1481
20. [20]
  F. Lei, W. Fan, X.K. Li, et al., Chin. Chem. Lett. 22 (2011) 831-834. doi: 10.1016/j.cclet.2010.12.056
21. [21]
  X.Y. Wu, X.C. Li, J. Mi, et al., Chin. Chem. Lett. 24 (2013) 117-119. doi: 10.1016/j.cclet.2013.01.022
22. [22]
  C. Fernandez, O. Nieto, E. Rivas, et al., Carbohydr. Res. 327 (2000) 353-365. doi: 10.1016/S0008-6215(00)00073-2
23. [23]
  M. Mueckler, C. Makepeace, J. Biol. Chem. 283 (2008) 11550-11555. doi: 10.1074/jbc.M708896200
24. [24]
  S.J. Vannucci, L.B. Seaman, R.C. Vannucci, J. Cereb, Blood Flow Metab.16 (1996) 77-81.
25. [25]
  G.V. Born, M.J. Cross, J. Physiol. 168 (1963) 178-195. doi: 10.1113/jphysiol.1963.sp007185
26. [26]
  M. Agrawal, V. Kumar, A.K. Singh, et al., ACS Chem. Neurosci. 4 (2013) 285-294. doi: 10.1021/cn300143m
27. [27]
  W.M. Pardridge, NeuroRx 2 (2005) 3-14. doi: 10.1602/neurorx.2.1.3
28. [28]
  W.M. Pardridge, Mol. Interv. 3 (2003) 90-105. doi: 10.1124/mi.3.2.90
29. [29]
  J. Li, S.F. Xu, Y. Peng, et al., Acta Pharmacol. Sin. 39 (2018) 275-285. doi: 10.1038/aps.2017.90
30. [30]
  H.Siebeneicher, A.Cleve, H.Rehwinkel, et al., ChemMedChem 11 (2016)2261-2271. doi: 10.1002/cmdc.201600276
1. [1]
  Erzhuo Cheng , Yunyi Li , Wei Yuan , Wei Gong , Yanjun Cai , Yuan Gu , Yong Jiang , Yu Chen , Jingxi Zhang , Guangquan Mo , Bin Yang . Galvanostatic method assembled ZIFs nanostructure as novel nanozyme for the glucose oxidation and biosensing. Chinese Chemical Letters, 2024, 35(9): 109386-. doi: 10.1016/j.cclet.2023.109386
2. [2]
  Han Wu , Yumei Wang , Zekai Ren , Hailin Cong , Youqing Shen , Bing Yu . The nanocarrier strategy for crossing the blood-brain barrier in glioma therapy. Chinese Chemical Letters, 2025, 36(4): 109996-. doi: 10.1016/j.cclet.2024.109996
3. [3]
  Lei Shen , Hongmei Liu , Ming Jin , Jinchao Zhang , Caixia Yin , Shuxiang Wang , Yutao Yang . “Three-in-one” strategy of trifluoromethyl regulated blood-brain barrier permeable fluorescent probe for peroxynitrite and antiepileptic evaluation of edaravone. Chinese Chemical Letters, 2024, 35(10): 109572-. doi: 10.1016/j.cclet.2024.109572
4. [4]
  Weijian Zhang , Xianyu Deng , Liying Wang , Jian Wang , Xiuting Guo , Lianggui Huang , Xinyi Wang , Jun Wu , Linjia Jiang . Poly(ferulic acid) nanocarrier enhances chemotherapy sensitivity of acute myeloid leukemia by selectively targeting inflammatory macrophages. Chinese Chemical Letters, 2024, 35(9): 109422-. doi: 10.1016/j.cclet.2023.109422
5. [5]
  Tao Long , Peng Chen , Bin Feng , Caili Yang , Kairong Wang , Yulei Wang , Can Chen , Yaping Wang , Ruotong Li , Meng Wu , Minhuan Lan , Wei Kong Pang , Jian-Fang Wu , Yuan-Li Ding . Reinforced concrete-like Na_3.5V_1.5Mn_0.5(PO₄)₃@graphene hybrids with hierarchical porosity as durable and high-rate sodium-ion battery cathode. Chinese Chemical Letters, 2024, 35(4): 109267-. doi: 10.1016/j.cclet.2023.109267
6. [6]
  Jiahui Li , Qiao Shi , Ying Xue , Mingde Zheng , Long Liu , Tuoyu Geng , Daoqing Gong , Minmeng Zhao . The effects of in ovo feeding of selenized glucose on liver selenium concentration and antioxidant capacity in neonatal broilers. Chinese Chemical Letters, 2024, 35(6): 109239-. doi: 10.1016/j.cclet.2023.109239
7. [7]
  Yue Sun , Yingnan Zhu , Jiahang Si , Ruikang Zhang , Yalan Ji , Jinjie Fan , Yuze Dong . Glucose-activated nanozyme hydrogels for microenvironment modulation via cascade reaction in diabetic wound. Chinese Chemical Letters, 2025, 36(4): 110012-. doi: 10.1016/j.cclet.2024.110012
8. [8]
  Kezuo Di , Jie Wei , Lijun Ding , Zhiying Shao , Junling Sha , Xilong Zhou , Huadong Heng , Xujing Feng , Kun Wang . A wearable sensor device based on screen-printed chip with biofuel cell-driven electrochromic display for noninvasive monitoring of glucose concentration. Chinese Chemical Letters, 2025, 36(2): 109911-. doi: 10.1016/j.cclet.2024.109911
9. [9]
  Zhen Liu , Zhi-Yuan Ren , Chen Yang , Xiangyi Shao , Li Chen , Xin Li . Asymmetric alkenylation reaction of benzoxazinones with diarylethylenes catalyzed by B(C₆F₅)₃/chiral phosphoric acid. Chinese Chemical Letters, 2024, 35(5): 108939-. doi: 10.1016/j.cclet.2023.108939
10. [10]
  Jisheng Liu , Junli Chen , Xifeng Zhang , Yin Wu , Xin Qi , Jie Wang , Xiang Gao . Red blood cell membrane-coated FLT3 inhibitor nanoparticles to enhance FLT3-ITD acute myeloid leukemia treatment. Chinese Chemical Letters, 2024, 35(9): 109779-. doi: 10.1016/j.cclet.2024.109779
11. [11]
  Long TANG , Yaxin BIAN , Luyuan CHEN , Xiangyang HOU , Xiao WANG , Jijiang WANG . Syntheses, structures, and properties of three coordination polymers based on 5-ethylpyridine-2,3-dicarboxylic acid and N-containing ligands. Chinese Journal of Inorganic Chemistry, 2024, 40(10): 1975-1985. doi: 10.11862/CJIC.20240180
12. [12]
  Jingtai Bi , Yupeng Cheng , Mengmeng Sun , Xiaofu Guo , Shizhao Wang , Yingying Zhao . Efficient and selective photocatalytic nitrite reduction to N₂ through CO₂ anion radical by eco-friendly tartaric acid activation. Chinese Chemical Letters, 2024, 35(11): 109639-. doi: 10.1016/j.cclet.2024.109639
13. [13]
  Xun Zhu , Chenchen Zhang , Yingying Li , Yin Lu , Na Huang , Dawei Wang . Degradation of perfluorooctanoic acid by inductively heated Fenton-like process over the Fe₃O₄/MIL-101 composite. Chinese Chemical Letters, 2024, 35(12): 109753-. doi: 10.1016/j.cclet.2024.109753
14. [14]
  Junying LI , Xinyan CHEN , Xihui DIAO , Muhammad Yaseen , Chao CHEN , Hao WANG , Chuansong QI , Wei LI . Chiral fluorescent sensor Tb³⁺@Cd-CP based on camphoric acid for the enantioselective recognition of R- and S-propylene glycol. Chinese Journal of Inorganic Chemistry, 2024, 40(12): 2497-2504. doi: 10.11862/CJIC.20240084
15. [15]
  Yuexiang Liu , Xiangqiao Yang , Tong Lin , Guantian Yang , Xiaoyong Xu , Bubing Zeng , Zhong Li , Weiping Zhu , Xuhong Qian . Efficient continuous synthesis of 2-[3-(trifluoromethyl)phenyl]malonic acid, a key intermediate of Triflumezopyrim, coupling with esterification-condensation-hydrolysis. Chinese Chemical Letters, 2025, 36(1): 109747-. doi: 10.1016/j.cclet.2024.109747
16. [16]
  Ao Sun , Zipeng Li , Shuchun Li , Xiangbao Meng , Zhongtang Li , Zhongjun Li . Stereoselective synthesis of α-3-deoxy-D-manno-oct-2-ulosonic acid (α-Kdo) derivatives using a C3-p-tolylthio-substituted Kdo fluoride donor. Chinese Chemical Letters, 2025, 36(3): 109972-. doi: 10.1016/j.cclet.2024.109972
17. [17]
  Runze Liu , Yankai Bian , Weili Dai . Qualitative and quantitative analysis of Brønsted and Lewis acid sites in zeolites: A combined probe-assisted 1H MAS NMR and NH3-TPD investigation. Chinese Journal of Structural Chemistry, 2024, 43(4): 100250-100250. doi: 10.1016/j.cjsc.2024.100250
18. [18]
  Le Ye , Wei-Xiong Zhang . Structural phase transition in a new organic-inorganic hybrid post-perovskite: (N,N-dimethylpyrrolidinium)[Mn(N(CN)2)3]. Chinese Journal of Structural Chemistry, 2024, 43(6): 100257-100257. doi: 10.1016/j.cjsc.2024.100257
19. [19]
  Jing Guo , Zhi-Guo Lu , Rui-Chen Zhao , Bao-Ku Li , Xin Zhang . Nucleic acid therapy for metabolic-related diseases. Chinese Chemical Letters, 2025, 36(3): 109875-. doi: 10.1016/j.cclet.2024.109875
20. [20]
  Ke Zhang , Yajing Wei , Linhua Xie , Sha Kang , Fei Li , Chuanyi Wang . Amorphous titanium carbide on N-defective g-C₃N₅ for high-efficiency photocatalytic NO removal. Chinese Chemical Letters, 2025, 36(3): 110086-. doi: 10.1016/j.cclet.2024.110086

Get Citation

PDF

XML

Metrics

PDF Downloads(3)
Abstract views(980)
HTML views(92)

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142