Citation: Yinghong Li, Yuanhui Zhang, Tianyu Niu, Yudong Pang, Yulong Shi, Qingxuan Zeng, Jingpu Zhang, Jingyang Zhu, Xiuli Zhong, Yanxiang Wang, Yan Wang, Sheng Tang, Weijia Kong, Danqing Song, Jiandong Jiang. Discovery and development of tricyclic matrinic derivatives as anti-diabetic candidates by AMPKα activation[J]. Chinese Chemical Letters, ;2023, 34(1): 107561. doi: 10.1016/j.cclet.2022.05.075 shu

Discovery and development of tricyclic matrinic derivatives as anti-diabetic candidates by AMPKα activation

Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China

kongweijia@imb.pumc.edu.cn

songdanqing@imb.pumc.edu.cn

jiang.jdong@163.com

Received Date: 19 January 2022
Revised Date: 9 May 2022
Accepted Date: 23 May 2022
Available Online: 27 May 2022

Figures(7)

We found compound 12N-p-trifluoromethylbenzenesulfonyl matrinane (1) was a potent anti-diabetic agent. Thirty-five tricyclic matrinic derivatives were synthesized and determined for their stimulatory effects on glucose consumption in L6 myotubes, taking 1 as the lead. In high-fat diet (HFD) and STZ induced diabetic mice, 9a significantly lowers blood glucose, improves glucose tolerance, and especially alleviates diabetic nephropathy and islet damage. Mechanism study indicates that 9a simultaneously targets mitochondrial complex I to increase AMP/ATP ratio, as well as liver kinase B1 (LKB1) and calcium/calmodulin-dependent protein kinase (CaMKK), which synergistically activates AMPKα and then stimulates glucose transporter 4 (GLUT4) membrane translocation and 2-deoxyglucose (2-DG) uptake to exert anti-diabetic efficacy. Therefore, compound 9a with a novel structure is a promising anti-diabetic candidate with the advantage of multiple-target mechanism, worthy of further investigation.
- Tricyclic matrinic derivatives,
- Glucose consumption,
- Diabetes mellitus,
- AMP-activated protein kinase (AMPK)
1. [1]
  E.M. Vaughan, J.J. Rueda, S.L. Samson, et al., Curr. Diabetes Rev. 16 (2020) 851–858. doi: 10.2174/1573399816666200206112318
2. [2]
  Z.G. Sun, Z.N. Li, H.L. Zhu, Mini Rev. Med. Chem. 20 (2020) 1709–1718. doi: 10.2174/1389557520666200628032507
3. [3]
  S. Cornell, J. Clin. Pharm. Ther. 45 (Suppl. 1) (2020) 17–27. doi: 10.1111/jcpt.13230
4. [4]
  E. Brown, H.J.L. Heerspink, D.J. Cuthbertson, et al., Lancet 398(2021) 262–276. doi: 10.1016/S0140-6736(21)00536-5
5. [5]
  G. Savarese, B. Schrage, F. Cosentino, et al., ESC Heart Fail. 7 (2020) 3438–3451. doi: 10.1002/ehf2.12937
6. [6]
  M. Singh, A. Kumar, Curr. Drug Saf. 13 (2018) 84–91. doi: 10.2174/1574886313666180226103408
7. [7]
  S. Tang, C. Wang, Y.H. Li, et al., Eur. J. Med. Chem. 201 (2020) 112315. doi: 10.1016/j.ejmech.2020.112315
8. [8]
  S. Tang, Y.H. Li, X.Y. Cheng, et al., Future Med. Chem. 8 (2016) 495–508. doi: 10.4155/fmc-2015-0019
9. [9]
  X.Y. Cheng, Y.H. Li, S. Tang, et al., Eur. J. Med. Chem. 126 (2017) 133–142. doi: 10.1016/j.ejmech.2016.09.097
10. [10]
  S.G. Wang, L.Y. Kong, Y.H. Li, et al., Bioorg. Med. Chem. Lett. 25 (2015) 3690–3693. doi: 10.1016/j.bmcl.2015.06.043
11. [11]
  T. Niu, X. Zhao, J. Jiang, et al., Molecules. 24 (2019) 921. doi: 10.3390/molecules24050921
12. [12]
  J. Jiang, X. Zhao, T. Niu, et al., Pharmazie 74(2019) 265–269. doi: 10.1001/jamainternmed.2018.5295
13. [13]
  S. Tang, Z.G. Peng, X. Zhang, et al., Chin. Chem. Lett. 27 (2016) 1052–1057. doi: 10.1016/j.cclet.2016.03.006
14. [14]
  F. Dehghan, F. Hajiaghaalipour, A. Yusof, et al., Sci. Rep. 6 (2016) 25139. doi: 10.1038/srep25139
15. [15]
  J.O. Lee, S.K. Lee, J.H. Kim, et al., J. Biol. Chem. 287 (2012) 44121–44129. doi: 10.1074/jbc.M112.361386
16. [16]
  S. Herzig, R.J. Shaw, Cell Biol. 19 (2018) 121–135. doi: 10.1038/nrm.2017.95
17. [17]
  A. Gormand, E. Henriksson, K. Ström, et al., J. Cell Biochem. 112 (2011) 1364–1375. doi: 10.1002/jcb.23053
18. [18]
  K. Fiedorczuk, L.A. Sazanov, Trends Cell Biol. 28 (2018) 835–867. doi: 10.1016/j.tcb.2018.06.006
19. [19]
  H. Zhu, B. Zhang, N. Zhu, et al., Chin. Chem. Lett. 32 (2021) 1220–1223. doi: 10.1016/j.cclet.2020.09.003
20. [20]
  J. Han, J. Yi, F. Liang, et al., Mol. Cell Endocrinol. 405 (2015) 63–73. doi: 10.1016/j.mce.2015.02.008
1. [1]
  Yanjing Li , Jiayin Li , Yuqi Chang , Yunfeng Lin , Lei Sui . Tetrahedral framework nucleic acids promote the proliferation and differentiation potential of diabetic bone marrow mesenchymal stem cell. Chinese Chemical Letters, 2024, 35(9): 109414-. doi: 10.1016/j.cclet.2023.109414
2. [2]
  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
3. [3]
  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
4. [4]
  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
5. [5]
  Cailiang Yue , Nan Sun , Yixing Qiu , Linlin Zhu , Zhiling Du , Fuqiang Liu . A direct Z-scheme 0D α-Fe₂O₃/TiO₂ heterojunction for enhanced photo-Fenton activity with low H₂O₂ consumption. Chinese Chemical Letters, 2024, 35(12): 109698-. doi: 10.1016/j.cclet.2024.109698
6. [6]
  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
7. [7]
  Ping Sun , Yuanqin Huang , Shunhong Chen , Xining Ma , Zhaokai Yang , Jian Wu . Indole derivatives as agrochemicals: An overview. Chinese Chemical Letters, 2024, 35(7): 109005-. doi: 10.1016/j.cclet.2023.109005
8. [8]
  Qiuyun Li , Yannan Zhu , Yining Wang , Gang Qi , Wen-Juan Hao , Kelu Yan , Bo Jiang . Catalytic CH activation-initiated transdiannulation: An oxygen transfer route to ring-fluorinated tricyclic γ-lactones. Chinese Chemical Letters, 2024, 35(9): 109494-. doi: 10.1016/j.cclet.2024.109494
9. [9]
  Fangwen Peng , Zhen Luo , Yingjin Ma , Haibo Ma . Theoretical study of aromaticity reversal in dimethyldihydropyrene derivatives. Chinese Journal of Structural Chemistry, 2024, 43(5): 100273-100273. doi: 10.1016/j.cjsc.2024.100273
10. [10]
  Zimo Yang , Yan Tong , Yongbo Liu , Qianlong Liu , Zhihao Ni , Yuna He , Yu Rao . Developing selective PI3K degraders to modulate both kinase and non-kinase functions. Chinese Chemical Letters, 2024, 35(11): 109577-. doi: 10.1016/j.cclet.2024.109577
11. [11]
  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
12. [12]
  Yadan SUN , Xinfeng LI , Qiang LIU , Oshio Hiroki , Yinshan MENG . Structures and magnetism of dinuclear Co complexes based on imine derivatives. Chinese Journal of Inorganic Chemistry, 2024, 40(11): 2212-2220. doi: 10.11862/CJIC.20240131
13. [13]
  Zhuwen Wei , Jiayan Chen , Congzhen Xie , Yang Chen , Shifa Zhu . Divergent de novo construction of α-functionalized pyrrole derivatives via coarctate reaction. Chinese Chemical Letters, 2024, 35(12): 109677-. doi: 10.1016/j.cclet.2024.109677
14. [14]
  Fei-Yan Gao , Yan Wu , Ling Yang , Zhong-Yi Ma , Yi Chen , Xiao-Man Mao , Xu-Fei Bian , Pei Tang , Chong Li . Orally delivered berberine derivatives for dual therapy in diabetic complications with MRSA infections. Chinese Chemical Letters, 2025, 36(4): 109917-. doi: 10.1016/j.cclet.2024.109917
15. [15]
  Shuying Li , Weiwei ZhuGe , Xuan Sun , Chongzhen Sun , Zhaojun Liu , Chenghe Xiong , Min Xiao , Guofeng Gu . Convergent synthesis and immunological study of oligosaccharide derivatives related to galactomannan from Antrodia cinnamomea. Chinese Chemical Letters, 2024, 35(5): 109089-. doi: 10.1016/j.cclet.2023.109089
16. [16]
  Tao Wei , Jiahao Lu , Pan Zhang , Qi Zhang , Guang Yang , Ruizhi Yang , Daifen Chen , Qian Wang , Yongfu Tang . An intermittent lithium deposition model based on bimetallic MOFs derivatives for dendrite-free lithium anode with ultrahigh areal capacity. Chinese Chemical Letters, 2024, 35(8): 109122-. doi: 10.1016/j.cclet.2023.109122
17. [17]
  Sifan Du , Yuan Wang , Fulin Wang , Tianyu Wang , Li Zhang , Minghua Liu . Evolution of hollow nanosphere to microtube in the self-assembly of chiral dansyl derivatives and inversed circularly polarized luminescence. Chinese Chemical Letters, 2024, 35(7): 109256-. doi: 10.1016/j.cclet.2023.109256
18. [18]
  Jun-Ming Cao , Kai-Yang Zhang , Jia-Lin Yang , Zhen-Yi Gu , Xing-Long Wu . Differential bonding behaviors of sodium/potassium-ion storage in sawdust waste carbon derivatives. Chinese Chemical Letters, 2024, 35(4): 109304-. doi: 10.1016/j.cclet.2023.109304
19. [19]
  Kuan Deng , Fei Yang , Zhi-Qi Cheng , Bi-Wen Ren , Hua Liu , Jiao Chen , Meng-Yao She , Le Yu , Xiao-Gang Liu , Hai-Tao Feng , Jian-Li Li . Construction of wavelength-tunable DSE quinoline salt derivatives by regulating the hybridization form of the nitrogen atom and intramolecular torsion angle. Chinese Chemical Letters, 2024, 35(10): 109464-. doi: 10.1016/j.cclet.2023.109464
20. [20]
  Liping Zhao , Xixi Guo , Zhimeng Zhang , Xi Lu , Qingxuan Zeng , Tianyun Fan , Xintong Zhang , Fenbei Chen , Mengyi Xu , Min Yuan , Zhenjun Li , Jiandong Jiang , Jing Pang , Xuefu You , Yanxiang Wang , Danqing Song . Novel berberine derivatives as adjuvants in the battle against Acinetobacter baumannii: A promising strategy for combating multi-drug resistance. Chinese Chemical Letters, 2024, 35(10): 109506-. doi: 10.1016/j.cclet.2024.109506

Get Citation

PDF

XML

Metrics

PDF Downloads(4)
Abstract views(657)
HTML views(69)

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