Citation: Xue-Yuan Jin, Shi-Yong Fan, Hong-Wu Li, Wei-Guo Shi, Wei Chen, Hui-Fen Wang, Bo-Hua Zhong. Novel liver-specific nitric oxide (NO) releasing drugs with bile acid as both NO carrier and targeting ligand[J]. Chinese Chemical Letters, ;2014, 25(05): 787-790. doi: 10.1016/j.cclet.2014.04.001 shu

Novel liver-specific nitric oxide (NO) releasing drugs with bile acid as both NO carrier and targeting ligand

1.
a Chinese PLA General Hospital & Chinese PLA Medical School, Beijing 100853, China;
2.
b Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China

Corresponding author: Hui-Fen Wang, Bo-Hua Zhong,
Received Date: 6 January 2014
Available Online: 24 March 2014
Fund Project: National Natural Science Foundation of China (Nos. 30572220 and 30972626). (863)

Novel liver-specific nitric oxide (NO) releasing drugs with bile acid as both the NO carrier and targeting ligand were designed and synthesized by direct nitration of the hydroxyl group in bile acids or the 3-O-hydroxyl alkyl derivatives, with the intact 24-COOH being preserved for hepatocyte specific recognition. Preliminary biological evaluation revealed that oral administrated targeted conjugates could protect mice against acute liver damage induced by acetaminophen or carbon tetrachloride. The nitrate level in the liver significantly increased after oral administration of 1e while nitrate level in the blood did not significantly change. Co-administration of ursodeoxycholic acid (UDCA) significantly antagonized the increase of nitrate in the liver resulted by administration of 1e.
- Liver-specific,
- Nitric oxide releasing drugs,
- Hepatoprotective activity,
- Bile acid
1. [1]
  [1] D.C. Rockey, V. Shah, Nitric oxide biology and the liver: report of an AASLD research workshop, Hepatology 39 (2004) 250-257.
2. [2]
  [2] M. Abu-Amara, S.Y. Yang, A. Seifalian, B. Davidson, B. Fuller, The nitric oxide pathway-evidence and mechanisms for protection against liver ischaemia reperfusion injury, Liver. Int. 32 (2012) 531-543.
3. [3]
  [3] N.M. Atucha, F.J. Nadal, D. Iyu, et al., Role of vascular nitric oxide in experimental liver cirrhosis, Curr. Vasc. Pharmacol. 3 (2005) 81-85.
4. [4]
  [4] L. Bellis, A. Berzigotti, J.G. Abraldes, et al., Low doses of isosorbide mononitrate attenuate the postprandial increase in portal pressure in patients with cirrhosis, Hepatology 37 (2003) 378-384.
5. [5]
  [5] A. Enhsen, W. Kramer, G. Wess, Bile acids in drug discovery, Drug Discov. Today 3 (1998) 409-418.
6. [6]
  [6] J. Li, L. Hai, W.J. Liu, X.C. Wu, Y. Wu, Study on synthesis and distribution in vivo of 5-Fu-cholic acid conjugate, Chin. Chem. Lett. 20 (2009) 136-138.
7. [7]
  [7] S. Fiorucci, E. Antonelli, E. Distrutti, et al., Liver delivery of NO by NCX-1000 protects against acute liver failure and mitochondrial dysfunction induced by APAP in mice, Br. J. Pharmacol. 143 (2004) 33-42.
8. [8]
  [8] S. Fiorucci, A. Mencarelli, B. Palazzetti, et al., An NO derivative of ursodeoxycholic acid protects against Fas-mediated liver injury by inhibiting caspase activity, Proc. Natl. Acad. Sci. U.S.A. 98 (2001) 2652-2657.
9. [9]
  [9] D.P. Soldato, S.A. Nicox, Pharmaceutical compounds, Patent WO 0061604, 2000- 10-19.
10. [10]
  [10] Data for new compounds. 1a: Yield 73%. Mp: 221-223 ℃; ¹H NMR (400 MHz, DMSO-d₆): δ 11.93 (s, 1H), 5.29 (s, 1H) 5.07 (s, 1H), 4.79 (s, 1H), 2.39-2.37 (m, 1H), 2.26-2.23 (m, 1H), 2.23-1.02 (m, 28 H), 0.81 (s, 3H). MS (FAB): m/z 542.6 (M-1). 1b: Yield 76%. Mp: 191-193 ℃; ¹H NMR (400 MHz, DMSO-d₆): δ 11.98 (s, 1H), 5.39 (s, 1H), 5.09 (s, 1H), 3.24 (s, 1H), 1.98-0.97 (m, 23H), 0.99-0.78 (m, 11H). MS (FAB): m/z 497.7 (M-1). 1c: Yield 67%. Mp: 218-220 ℃; ¹H NMR (400 MHz, DMSO-d₆): δ 11.93 (s, 1H), 4.85 (s, 1H), 4.20-4.18 (d, 2H), 3.79 (s, 1H), 3.63 (s, 1H), 1.99-0.97 (m, 30H), 0.59 (s, 3H). MS (FAB): m/z 452.5 (M-1). 1d: Yield 62%. Mp: 186-188 ℃; ¹H NMR (400 MHz, DMSO-d6): δ 11.84 (s, 1H), 4.85 (s, 1H), 3.60- 3.57 (d, 2H), 2.24 (s, 1H), 2.02-0.97 (m, 25H), 0.94 (d, 3H, J = 6.5 Hz), 0.85 (s, 3H), 0.63 (s, 3H). MS (FAB): m/z 436.4 (M-1). 1e: Yield 47%. Mp: 185-187 ℃; ¹H NMR (400 MHz, CDCl3): δ 11.96 (s, 1H), 4.56-4.52 (t, 2H), 3.86-3.84 (d, 1H, J = 7.0 Hz), 3.48 (s, 1H), 3.34-3.32 (t, 2H), 2.25-0.87 (m, 37H), 0.62 (s, 3H). MS (FAB): m/z 508.8 (M-1). 1f: Yield 43%. Mp: 174-176 ℃; ¹H NMR (400 MHz, CDCl₃): δ 12.05 (s, 1H), 4.56-4.54 (t, 2H), 3.90-3.87 (d, 1H, J = 6.8 Hz), 3.46 (s, 1H), 3.31-3.28 (t, 2H), 2.26-1.04 (m, 27H), 0.97 (s, 3H), 0.89 (d, 3H, J = 6.4 Hz), 0.61 (s, 3H). MS (FAB): m/z 480.5 (M-1).
11. [11]
  [11] M.D. Lu, X. Zhou, Y.J. Yu, et al., Synthesis and in vitro biological evaluation of nitric oxide-releasing derivatives of hydroxylcinnamic acids as anti-tumor agents, Chin. Chem. Lett. 24 (2013) 415-418.
12. [12]
  [12] Z. Xiang, Y.P. Chen, K.F. Ma, et al., The role of Ursodeoxycholic acid in nonalcoholic steatohepatitis: a systematic review, BMC Gastroenterol. 13 (2013) 140.
1. [1]
  Hao Cai , Xiaoyan Wu , Lei Jiang , Feng Yu , Yuxiang Yang , Yan Li , Xian Zhang , Jian Liu , Zijian Li , Hong Bi . Lysosome-targeted carbon dots with a light-controlled nitric oxide releasing property for enhanced photodynamic therapy. Chinese Chemical Letters, 2024, 35(4): 108946-. doi: 10.1016/j.cclet.2023.108946
2. [2]
  Guoping Yang , Zhoufu Lin , Xize Zhang , Jiawei Cao , Xuejiao Chen , Yufeng Liu , Xiaoling Lin , Ke Li . Assembly of Y(Ⅲ)-containing antimonotungstates induced by malic acid with catalytic activity for the synthesis of imidazoles. Chinese Chemical Letters, 2024, 35(12): 110274-. doi: 10.1016/j.cclet.2024.110274
3. [3]
  Yiyue Ding , Qiuxiang Zhang , Lei Zhang , Qilu Yao , Gang Feng , Zhang-Hui Lu . Exceptional activity of amino-modified rGO-immobilized PdAu nanoclusters for visible light-promoted dehydrogenation of formic acid. Chinese Chemical Letters, 2024, 35(7): 109593-. doi: 10.1016/j.cclet.2024.109593
4. [4]
  Xinyi Hu , Riguang Zhang , Zhao Jiang . Depositing the PtNi nanoparticles on niobium oxide to enhance the activity and CO-tolerance for alkaline methanol electrooxidation. Chinese Journal of Structural Chemistry, 2023, 42(11): 100157-100157. doi: 10.1016/j.cjsc.2023.100157
5. [5]
  Chaozheng He , Jia Wang , Ling Fu , Wei Wei . Nitric oxide assists nitrogen reduction reaction on 2D MBene: A theoretical study. Chinese Chemical Letters, 2024, 35(5): 109037-. doi: 10.1016/j.cclet.2023.109037
6. [6]
  Guangyao Wang , Zhitong Xu , Ye Qi , Yueguang Fang , Guiling Ning , Junwei Ye . Electrospun nanofibrous membranes with antimicrobial activity for air filtration. Chinese Chemical Letters, 2024, 35(10): 109503-. doi: 10.1016/j.cclet.2024.109503
7. [7]
  Qian Wang , Yeping Bian , Gagan Dhawan , Wei Zhang , Alexander E. Sorochinsky , Ata Makarem , Vadim A. Soloshonok , Jianlin Han . FDA approved fluorine-containing drugs in 2023. Chinese Chemical Letters, 2024, 35(11): 109780-. doi: 10.1016/j.cclet.2024.109780
8. [8]
  Feihu Wu , Gengwen Chen , Kaitao Lai , Shiqing Zhang , Yingchao Liu , Ruijian Luo , Xiaocong Wang , Pinzhi Cao , Yi Ye , Jiarong Lian , Junle Qu , Zhigang Yang , Xiaojun Peng . Non-specific/specific SERS spectra concatenation for precise bacteria classifications with few samples using a residual neural network. Chinese Chemical Letters, 2025, 36(1): 109884-. doi: 10.1016/j.cclet.2024.109884
9. [9]
  Ting Wang , Xin Yu , Yaqiang Xie . Unlocking stability: Preserving activity of biomimetic catalysts with covalent organic framework cladding. Chinese Chemical Letters, 2024, 35(6): 109320-. doi: 10.1016/j.cclet.2023.109320
10. [10]
  Fangping Yang , Jin Shi , Yuansong Wei , Qing Gao , Jingrui Shen , Lichen Yin , Haoyu Tang . Mixed-charge glycopolypeptides as antibacterial coatings with long-term activity. Chinese Chemical Letters, 2025, 36(2): 109746-. doi: 10.1016/j.cclet.2024.109746
11. [11]
  Chong Liu , Ling Li , Jiahui Gao , Yanwei Li , Nazhen Zhang , Jing Zang , Cong Liu , Zhaopei Guo , Yanhui Li , Huayu Tian . The study of antibacterial activity of cationic poly(β-amino ester) regulating by amphiphilic balance. Chinese Chemical Letters, 2025, 36(2): 110118-. doi: 10.1016/j.cclet.2024.110118
12. [12]
  Xiaohong Wen , Mei Yang , Lie Li , Mingmin Huang , Wei Cui , Suping Li , Haiyan Chen , Chen Li , Qiuping Guo . Enzymatically controlled DNA tetrahedron nanoprobes for specific imaging of ATP in tumor. Chinese Chemical Letters, 2024, 35(8): 109291-. doi: 10.1016/j.cclet.2023.109291
13. [13]
  Xing Tian , Di Wu , Wanheng Wei , Guifu Dai , Zhanxian Li , Benhua Wang , Mingming Yu . A lipid droplets-targetable fluorescent probe for polarity detection in cells of iron death, inflammation and fatty liver tissue. Chinese Chemical Letters, 2024, 35(6): 108912-. doi: 10.1016/j.cclet.2023.108912
14. [14]
  Qiang Li , Jiangbo Fan , Hongkai Mu , Lin Chen , Yongzhen Yang , Shiping Yu . Nucleus-targeting orange-emissive carbon dots delivery adriamycin for enhanced anti-liver cancer therapy. Chinese Chemical Letters, 2024, 35(6): 108947-. doi: 10.1016/j.cclet.2023.108947
15. [15]
  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
16. [16]
  Yingjie Wang , Peng Tang , Wenchao Tu , Qi Gao , Cuizhu Wang , Luying Tan , Lixin Zhao , Hongye Han , Liefeng Ma , Kouharu Otsuki , Weilie Xiao , Wenli Wang , Jinping Liu , Yong Li , Zhajun Zhan , Wei Li , Xianli Zhou , Ning Li . Highly anticipated natural diterpenoids as an important source of new drugs in 2013–2023. Chinese Chemical Letters, 2025, 36(1): 109955-. doi: 10.1016/j.cclet.2024.109955
17. [17]
  Wenyi Mei , Lijuan Xie , Xiaodong Zhang , Cunjian Shi , Fengzhi Wang , Qiqi Fu , Zhenjiang Zhao , Honglin Li , Yufang Xu , Zhuo Chen . Design, synthesis and biological evaluation of fluorescent derivatives of ursolic acid in living cells. Chinese Chemical Letters, 2024, 35(5): 108825-. doi: 10.1016/j.cclet.2023.108825
18. [18]
  Huipeng Zhao , Xiaoqiang Du . Polyoxometalates as the redox anolyte for efficient conversion of biomass to formic acid. Chinese Journal of Structural Chemistry, 2024, 43(2): 100246-100246. doi: 10.1016/j.cjsc.2024.100246
19. [19]
  Dan-Ying Xing , Xiao-Dan Zhao , Chuan-Shu He , Bo Lai . Kinetic study and DFT calculation on the tetracycline abatement by peracetic acid. Chinese Chemical Letters, 2024, 35(9): 109436-. doi: 10.1016/j.cclet.2023.109436
20. [20]
  Lihang Wang , Mary Li Javier , Chunshan Luo , Tingsheng Lu , Shudan Yao , Bing Qiu , Yun Wang , Yunfeng Lin . Research advances of tetrahedral framework nucleic acid-based systems in biomedicine. Chinese Chemical Letters, 2024, 35(11): 109591-. doi: 10.1016/j.cclet.2024.109591

Get Citation

PDF

XML

Metrics

PDF Downloads(0)
Abstract views(680)
HTML views(25)

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