Citation: Qing Tang, Kai Zhao, Hui-Hui Zhu, Qiang Lin, Hai-Yue Zhao, Wei-Xuan Zheng, Zhong-Nan Wu, Hao Wang, Guo-Cai Wang, Yu-Bo Zhang. Pecanthines A–C, unprecedented dimeric β-carboline alkaloids from the seeds of Peganum harmala[J]. Chinese Chemical Letters, ;2026, 37(10): 112172. doi: 10.1016/j.cclet.2025.112172 shu

Pecanthines A–C, unprecedented dimeric β-carboline alkaloids from the seeds of Peganum harmala

Qing Tang ^{a, b, 1} ,
Kai Zhao ^{a, b, 1} ,
Hui-Hui Zhu ^{a, b, 1} ,
Qiang Lin ^{a, b} ,
Hai-Yue Zhao ^{a, b} ,
Wei-Xuan Zheng ^{a, b} ,
Zhong-Nan Wu ^d ,
Hao Wang ^{a, *,} ,
Guo-Cai Wang ^{a, b, *,} ,
Yu-Bo Zhang ^{a, c, *,}

a.
State Key Laboratory of Bioactive Molecules and Druggability Assessment, and Department of Anesthesiology, The First Affiliated Hospital of Jinan University, Guangzhou 510632, China
b.
Institute of Traditional Chinese Medicine & Natural Products, Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou 510632, China
c.
Guangdong Clinical Translational Center for Targeted Drug, Department of Pharmacology, School of Medicine, Jinan University, Guangzhou 510632, China
d.
Guangdong Provincial Key Laboratory of Research and Development of Natural Drugs, School of Pharmacy, Guangdong Medical University, Dongguan 523808, China

haowang@jnu.edu.cn

twangguocai@jnu.edu.cn

ybzhang99@126.com

Received Date: 8 August 2025
Revised Date: 23 November 2025
Accepted Date: 25 November 2025
Available Online: 25 November 2025

Figures(7)

Three novel β-carboline alkaloid dimers, pecanthines A–C (1−3), featuring unprecedented 6/5/6/6–5/6 and 6/5/6/6/5/6 polycyclic frameworks, were isolated from the seeds of Peganum harmala. Their structures were elucidated by spectroscopic analyses and X-ray diffraction. Notably, compounds 1 and 2 represent the first heterodimeric alkaloids merging canthin-6-one and melatonin-type scaffolds, with 1 additionally displaying neuroprotective activity. In addition, a gram-scale synthesis of 3 was achieved in six steps, leveraging a key acyl-ketene imine condensation and Suzuki coupling. Biological evaluation revealed that 3 acts as a new topoisomerase Ⅰ (Topo Ⅰ) inhibitor, exhibiting remarkable antiproliferative activity. Mechanistic studies demonstrated that 3 induces DNA damage, triggering apoptosis and cell cycle arrest in cancer cells. The discovery and gram-scale synthesis of 3 provide a promising lead compound and a novel molecular scaffold for anticancer drug development.
- Peganum harmala,
- β-Carboline alkaloid,
- Structural revision,
- Topo Ⅰ inhibition,
- Neuroprotective activity
1. [1]
  Y. Pommier, Chem. Rev. 109 (2009) 2894–2902. doi: 10.1021/cr900097c
2. [2]
  Y. Pommier, A. Nussenzweig, S. Takeda, et al., Nat. Rev. Mol. Cell. Biol. 23 (2022) 407–427. doi: 10.1038/s41580-022-00452-3
3. [3]
  K. Hevener, T.A. Verstak, K.E. Lutat, et al., Acta. Pharm. Sin. B 8 (2018) 844–861. doi: 10.1016/j.apsb.2018.07.008
4. [4]
  A.M. Elshazly, P.A. Wright, J. Xu, et al., Autophagy Rep 2 (2023) 1–16. doi: 10.1080/27694127.2022.2155904
5. [5]
  F. Lei, Y. Xiong, Y. Wang, et al., J. Med. Chem. 65 (2022) 7975–7992. doi: 10.1021/acs.jmedchem.2c00520
6. [6]
  X. Deng, Y. Wang, X. Yang, et al., J. Med. Chem. 68 (2025) 3518–3546. doi: 10.1021/acs.jmedchem.4c02689
7. [7]
  H. Wang, X. Bai, Y. Huang, et al., Chin. Chem. Lett. 34 (2023) 107671. doi: 10.1016/j.cclet.2022.07.014
8. [8]
  X. Wei, Z.W. Luo, G.Q. Zhang, et al., Chin. Chem. Lett. 37 (2026) 111048. doi: 10.1016/j.cclet.2025.111048
9. [9]
  S. Kumar, M.Y. Sherman, Int. J. Mol. Sci. 24 (2023) 7233. doi: 10.3390/ijms24087233
10. [10]
  B. Wang, S. Wu, S. Jia, et al., J. Med. Chem. 67 (2024) 14155–14174. doi: 10.1021/acs.jmedchem.4c00982
11. [11]
  M. Cushman, J. Med. Chem. 64 (2021) 17572–17600. doi: 10.1021/acs.jmedchem.1c01491
12. [12]
  A. Beato, A. Gori, B. Boucherle, et al., J. Med. Chem. 64 (2021) 1392–1422. doi: 10.1021/acs.jmedchem.0c01887
13. [13]
  L. Yu, N. Shen, J. Ren, et al., Fitoterapia 180 (2025) 106326. doi: 10.1016/j.fitote.2024.106326
14. [14]
  Q. Liu, C. Yang, J. Qi, et al., Chem. Biodivers. 22 (2025) e202402953. doi: 10.1002/cbdv.202402953
15. [15]
  M.U. Rehman, Y. Zuo, N. Tu, et al., Eur. J. Med. Chem. 287 (2025) 117350.
16. [16]
  F.A. Khan, A. Maalik, Z. Iqbal, et al., Eur. J. Pharmacol. 721 (2013) 391–394. doi: 10.1016/j.ejphar.2013.05.003
17. [17]
  Y.L. Guo, J.W. Yu, Y. Cao, et al., Eur. J. Med. Chem. 265 (2024) 116061. doi: 10.1016/j.ejmech.2023.116061
18. [18]
  R. Cao, W. Peng, H. Chen, et al., Biochem. Biophys. Res. Commun. 338 (2005) 1557–1563. doi: 10.1016/j.bbrc.2005.10.121
19. [19]
  K.B. Wang, Y.T. Di, Y. Bao, et al., Org. Lett. 16 (2014) 4028–4031. doi: 10.1021/ol501856v
20. [20]
  K.B. Wang, D.H. Li, P. Hu, et al., Org. Lett. 18 (2016) 3398–3401. doi: 10.1021/acs.orglett.6b01560
21. [21]
  R. Cao, W. Peng, Z. Wang, et al., Curr. Med. Chem. 14 (2007) 479–500. doi: 10.2174/092986707779940998
22. [22]
  K.B. Wang, D.H. Li, Y. Bao, et al., J. Nat. Prod. 80 (2017) 551–559. doi: 10.1021/acs.jnatprod.6b01146
23. [23]
  S. Li, X. Cheng, C. Wang, J. Ethnopharmacol. 203 (2017) 127–162.
24. [24]
  Z.N. Wu, N.H. Chen, Q. Tang, et al., Org. Lett. 22 (2020) 7310–7314. doi: 10.1021/acs.orglett.0c02650
25. [25]
  Z.N. Wu, Y.B. Zhang, G.C. Wang, et al., Fitoterapia 179 (2024) 106237. doi: 10.1016/j.fitote.2024.106237
26. [26]
  Y. Liu, C. Liu, H. Guo, et al., Chin. Chem. Lett. 36 (2025) 110558.
27. [27]
  G. Cebrián-Torrejón, N. Mackiewicz, R.P. Vázquez-Manrique, et al., Eur. J. Org. Chem. 2013 (2013) 5821–5828. doi: 10.1002/ejoc.201300770
28. [28]
  J. Dai, N. Li, J. Wang, et al., Molecules 21 (2016) 493. doi: 10.3390/molecules21040493
29. [29]
  D. Scharnagel, J. Goller, N. Deibl, Angew. Chem. Int. Ed. 57 (2018) 2432–2435. doi: 10.1002/anie.201712852
30. [30]
  X. Zhang, Nat. Prod. Rep. 41 (2024) 784–812. doi: 10.1039/d3np00048f
31. [31]
  T.M. Lv, D.L. Chen, J.J. Liang, et al., Org. Lett. 23 (2021) 7231–7235. doi: 10.1021/acs.orglett.1c02626
32. [32]
  N. Pemberton, L. Jakobsson, F. Almqvist, Org. Lett. 8 (2006) 935–938. doi: 10.1021/ol052998e
1. [1]
  Yongjian Liu , Cen Liu , Haitao Guo , Jinchai Qi , Heng Chen , Yuping Yang , Tao Ma , Yonggang Liu . Alkaloids peganumiums A–C from Peganum harmala L., with two novel long conjugated structures. Chinese Chemical Letters, 2025, 36(8): 110558-. doi: 10.1016/j.cclet.2024.110558
2. [2]
  Ji-Ping Liao , Jiang Li , Wen-Jie Qin , Xiu-Mei Duan , Peng-Fei Wang , Jin-Ying Tian , Xiang Yuan , Pei-Cheng Zhang , Fei Ye , Ya-Nan Yang . Two racemic pairs of benzo bicyclo[3.3.1]/[4.2.1] nonene stilbenoid dimers from Heterosmilax yunnanensis and structural revision of syagrusin A. Chinese Chemical Letters, 2025, 36(9): 110687-. doi: 10.1016/j.cclet.2024.110687
3. [3]
  Chengyu JIANG , Xufeng LIU . Synthesis, structural characterization, electrocatalytic proton reduction, and fungicidal activity of thiazole-containing di-iron complexes. Chinese Journal of Inorganic Chemistry, 2026, 42(2): 355-364. doi: 10.11862/CJIC.20250253
4. [4]
  Xuan Pan , Tao Sheng , Zhanzhu Liu . A concise total synthesis of monoterpenoid indole alkaloid (-)-voacafricine A. Chinese Chemical Letters, 2025, 36(10): 110913-. doi: 10.1016/j.cclet.2025.110913
5. [5]
  Maitri Bhattacharjee , Rekha Boruah Smriti , R. N. Dutta Purkayastha , Waldemar Maniukiewicz , Shubhamoy Chowdhury , Debasish Maiti , Tamanna Akhtar . Synthesis, structural characterization, bio-activity, and density functional theory calculation on Cu(Ⅱ) complexes with hydrazone-based Schiff base ligands. Chinese Journal of Inorganic Chemistry, 2024, 40(7): 1409-1422. doi: 10.11862/CJIC.20240007
6. [6]
  Jiao-Zhen Zhang , Cheng-Min Zhang , Yong-Jie Wang , Pei-Lin Wu , Rui-Feng Liu , Ye Li , Ming-Zhu Zhu , Shuang-Zhi Yuan , Ze-Jun Xu , Hong-Xiang Lou . Revision of the absolute configurations of Pallavicinia diterpenoids and further discovery of their Diels−Alder cycloadducts. Chinese Chemical Letters, 2026, 37(1): 110919-. doi: 10.1016/j.cclet.2025.110919
7. [7]
  Jingping Hu , Jing Xu . Total synthesis of a putative yuzurimine-type Daphniphyllum alkaloid C₁₄–epi-deoxycalyciphylline H. Chinese Chemical Letters, 2024, 35(4): 108733-. doi: 10.1016/j.cclet.2023.108733
8. [8]
  Yu Liu , Lan Bao , Xiang Lyu , Zhonglin Wang , Zhengrun Chen , Jinhuan Dong , Xianxiu Xu , Zhongyan Hu . Divergent reactions of indolyl vinyl isonitriles: A facile access to skeletally diverse carboline-based biheteroaryls. Chinese Chemical Letters, 2026, 37(9): 112201-. doi: 10.1016/j.cclet.2025.112201
9. [9]
  Fanxin Kong , Hongzhi Wang , Huimei Duan . Inhibition effect of sulfation on Pt/TiO2 catalysts in methane combustion. Chinese Journal of Structural Chemistry, 2024, 43(5): 100287-100287. doi: 10.1016/j.cjsc.2024.100287
10. [10]
  Han Du , Shiyong Chu , Chunchen Zhang , Yanjiao Ma . Structural stress: A primary driver of structural degradation in Li-rich layered cathodes. Chinese Journal of Structural Chemistry, 2026, 45(1): 100730-100730. doi: 10.1016/j.cjsc.2025.100730
11. [11]
  Chenlu Huang , Xinyu Yang , Qingyu Yu , Linhua Zhang , Dunwan Zhu . Gas-generating polymersomes-based amplified photoimmunotherapy for abscopal effect and tumor metastasis inhibition. Chinese Chemical Letters, 2024, 35(6): 109680-. doi: 10.1016/j.cclet.2024.109680
12. [12]
  Yuanyi Zhou , Ke Ma , Jinfeng Liu , Zirun Zheng , Bo Hu , Yu Meng , Zhizhong Li , Mingshan Zhu . Is reactive oxygen species the only way for cancer inhibition over single atom nanomedicine? Autophagy regulation also works. Chinese Chemical Letters, 2024, 35(6): 109056-. doi: 10.1016/j.cclet.2023.109056
13. [13]
  Yuanzheng Wang , Chen Zhang , Shuyan Han , Xiaoli Kong , Changyun Quan , Jun Wu , Wei Zhang . Cancer cell membrane camouflaged biomimetic gelatin-based nanogel for tumor inhibition. Chinese Chemical Letters, 2024, 35(11): 109578-. doi: 10.1016/j.cclet.2024.109578
14. [14]
  Yanfei Liu , Yaqin Hu , Yifu Tan , Qiwen Chen , Zhenbao Liu . Tumor acidic microenvironment activatable DNA nanostructure for precise cancer cell targeting and inhibition. Chinese Chemical Letters, 2025, 36(1): 110289-. doi: 10.1016/j.cclet.2024.110289
15. [15]
  Qian Wang , Dong Yang , Wenxing Xin , Yongqi Wang , Wenchang Han , Wengxiang Yan , Chunman Yang , Fei Wang , Yiyong Zhang , Ziyi Zhu , Xue Li . Modulation of desolvation barriers and inhibition of lithium dendrites based on lithophilic electrolyte additives for lithium metal anode. Chinese Chemical Letters, 2025, 36(6): 110669-. doi: 10.1016/j.cclet.2024.110669
16. [16]
  Huijuan Zhang , Chenglin Liang , Xinyi Ding , Meng Zhang , Siyu Lu , Lin Hou . Manganese-based nano-delivery system for sensitized anti-tumor immunotherapy via combined autophagy inhibition. Chinese Chemical Letters, 2025, 36(7): 110525-. doi: 10.1016/j.cclet.2024.110525
17. [17]
  Lingdan Kong , Pingping Huang , Feng Yuan , Yue Zhang , Xiaoqian Shi , Kang Han , Keke Liu , Qing Xu , Wenjing Zhang , Tom Lawson , Xiaoru Xia , Yong Liu , Yuepeng Jin . A metal-free bionic nanozyme for efficient inhibition of cancer recurrence and metastasis following photothermal therapy. Chinese Chemical Letters, 2025, 36(9): 111030-. doi: 10.1016/j.cclet.2025.111030
18. [18]
  Ya-Jie Zhu , Zhi-Min Lv , Hao-Feng Zhu , Qi-Yan Qi , Shang-Bo Yu , Jia Tian , Wei Zhou , Zhan-Ting Li . Self-assembly of disassemblable supramolecular organic frameworks for doxorubicin delivery, photofrin posttreatment phototoxicity inhibition and heparin neutralization. Chinese Chemical Letters, 2026, 37(1): 111353-. doi: 10.1016/j.cclet.2025.111353
19. [19]
  Le Chen , Hui Wang , Yiyun Cheng . An erucin-anchored polymer with excellent amyloidosis inhibition and direct cell membrane penetration ability for intracellular protein delivery. Chinese Chemical Letters, 2026, 37(4): 111172-. doi: 10.1016/j.cclet.2025.111172
20. [20]
  Wei Zhang , Lei Yang , Zhihang Jin , Shusheng Zhang , Fawei Zhu , Zhanxian Li , Mingming Yu . Fluorescent probes reveal the differential impact of ferroptosis inhibition on drug-induced liver and kidney injury. Chinese Chemical Letters, 2026, 37(4): 111220-. doi: 10.1016/j.cclet.2025.111220

Get Citation

PDF

XML

Metrics

PDF Downloads(0)
Abstract views(3)
HTML views(0)

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