Citation: Lei Li, Xin-Ying Zhu, Jun-Yu Zhu, Zhi-Hao Wu, Yan-Jiang Zhang, Fang-Yu Yuan, Dong Huang, Sheng Yin, Gui-Hua Tang. Penispirolactam and penipyrroloindole, two unusual polycyclic indole diterpenoids with anti-hepatic fibrosis activity from the endophytic fungus Penicillium janthinellum H-6[J]. Chinese Chemical Letters, ;2026, 37(4): 111161. doi: 10.1016/j.cclet.2025.111161 shu

Penispirolactam and penipyrroloindole, two unusual polycyclic indole diterpenoids with anti-hepatic fibrosis activity from the endophytic fungus Penicillium janthinellum H-6

School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China

yinsh2@mail.sysu.edu.cn

tanggh5@mail.sysu.edu.cn

Received Date: 22 January 2025
Revised Date: 26 March 2025
Accepted Date: 28 March 2025
Available Online: 28 March 2025

Figures(7)

Penispirolactam (1) and penipyrroloindole (2), two highly modified paspaline-type indole diterpenoids (IDTs), along with three new (3–5) and two known (6 and 7) paspaline-type IDTs were obtained from the endophytic fungus Penicillium janthinellum H-6 guided by liquid chromatography-mass spectrometry (LC-MS)-based molecular network. Architecturally, penispirolactam (1) possesses a unique octacyclic skeleton (6/5/6/6/5/6/6/6) with a spiro core formed by the integration of a C₆–C₂ unit with the indole moiety, and penipyrroloindole (2) represents a rearranged octacyclic skeleton (6/5/6/5/5/6/6/6) with a pyrrolo[1,2-a]indole core fragment. Their structures, including absolute configurations, were established by detailed spectroscopic analysis, gauge-independent atomic orbital (GIAO) 1D nuclear magnetic resonance (NMR) (DP4+) calculation protocol, and electronic circular dichroism (ECD) calculation method. The plausible biosynthetic pathway of compounds 1 and 2 was also speculated. Additionally, the anti-hepatic fibrosis activity of all compounds was explored, and it was found that 1 could exert its effects by inhibiting the transforming growth factor-β (TGF-β)/Smad signaling pathway without cytotoxicity.
- Endophytic fungus,
- Penicillium janthinellum H-6,
- Paspaline-derived indole diterpenoid,
- Penispirolactam,
- Penipyrroloindole,
- Anti-hepatic fibrosis
1. [1]
  T. Rodrigues, D. Reker, P. Schneider, et al., Nat. Chem. 8 (2016) 531–541. doi: 10.1038/nchem.2479
2. [2]
  Y. Wang, P. Tang, W. Tu, et al., Chin. Chem. Lett. 36 (2025) 109955. doi: 10.1016/j.cclet.2024.109955
3. [3]
  J.G. Ondeyka, G.L. Helms, O.D. Hensens, et al., J. Am. Chem. Soc. 119 (1997) 8809–8816. doi: 10.1021/ja971664k
4. [4]
  W. Yang, T. Chen, Q. Tan, et al., J. Nat. Prod. 86 (2023) 1392–1401. doi: 10.1021/acs.jnatprod.2c01172
5. [5]
  F. Cao, X.M. Liu, X. Wang, et al., Bioorg. Chem. 141 (2023) 106863. doi: 10.1016/j.bioorg.2023.106863
6. [6]
  X.Z. Su, L.F. Zhang, K. Hu, et al., Angew. Chem. Int. Ed. 63 (2024) e202313859. doi: 10.1002/anie.202313859
7. [7]
  L.T. Dai, L. Yang, J.C. Guo, et al., Bioorg. Chem. 145 (2024) 107205. doi: 10.1016/j.bioorg.2024.107205
8. [8]
  J.W. Niu, J.Z. Qi, P.C. Wang, et al., Nat. Prod. Bioprospect. 13 (2023) 3. doi: 10.1007/s13659-022-00368-7
9. [9]
  C. Liu, A. Minami, T. Dairi, et al., Org. Lett. 18 (2016) 5026–5029. doi: 10.1021/acs.orglett.6b02482
10. [10]
  K. Tagami, C. Liu, A. Minami, et al., J. Am. Chem. Soc. 135 (2013) 1260–1263. doi: 10.1021/ja3116636
11. [11]
  L.D. Guo, Z. Xu, R. Tong, Angew. Chem. Int. Ed. 61 (2021) e202115384.
12. [12]
  M. Parola, M. Pinzani, Mol. Asp. Med. 65 (2019) 37–55. doi: 10.1016/j.mam.2018.09.002
13. [13]
  D.Y. Zhang, S.L. Friedman, Hepatology 56 (2012) 769–775. doi: 10.1002/hep.25670
14. [14]
  S. Li, L. Gan, Y.J. Tian, et al., Bioorg. Chem. 114 (2021) 105222. doi: 10.1016/j.bioorg.2021.105222
15. [15]
  L. Gan, Q. Jiang, D. Huang, et al., Nat. Chem. Biol. 21 (2024) 80–90.
16. [16]
  C. Matsui, Y. Ikeda, H. Iinuma, et al., J. Antibiot. 67 (2014) 787–790. doi: 10.1038/ja.2014.63
17. [17]
  T. Kawahara, A. Nagai, M. Takagi, et al., J. Antibiot. 65 (2012) 535–538. doi: 10.1038/ja.2012.64
18. [18]
  L.M. Zhou, F.D. Kong, P. Fan, et al., J. Nat. Prod. 82 (2019) 2638–2644. doi: 10.1021/acs.jnatprod.9b00620
19. [19]
  L. Xu, A.Y. Hui, E. Albanis, et al., Gut 54 (2005) 142–151. doi: 10.1136/gut.2004.042127
20. [20]
  E. Altrock, C. Sens, C. Wuerfel, et al., J. Hepatol. 62 (2015) 625–633. doi: 10.1016/j.jhep.2014.06.010
21. [21]
  G.J. Inman, F.J. Nicolas, J.F. Callahan, et al., Mol. Pharm. 62 (2002) 65–74. doi: 10.1124/mol.62.1.65
22. [22]
  J. Zhang, R. Li, Q. Liu, et al., Mol. Pharm. 17 (2020) 4152–4162. doi: 10.1021/acs.molpharmaceut.0c00633
23. [23]
  F. Xu, C. Liu, D. Zhou, et al., J. Histochem. Cytochem. 64 (2016) 157–167. doi: 10.1369/0022155415627681
24. [24]
  J. Massagué, Nat. Rev. Mol. Cell Biol. 13 (2012) 616–630. doi: 10.1038/nrm3434
1. [1]
  Aimin Fu , Chunmei Chen , Qin Li , Nanjin Ding , Jiaxin Dong , Yu Chen , Mengsha Wei , Weiguang Sun , Hucheng Zhu , Yonghui Zhang . Niduenes A−F, six functionalized sesterterpenoids with a pentacyclic 5/5/5/5/6 skeleton from endophytic fungus Aspergillus nidulans. Chinese Chemical Letters, 2024, 35(9): 109100-. doi: 10.1016/j.cclet.2023.109100
2. [2]
  Hong Zhang , Cui-Ping Li , Li-Li Wang , Zhuo-Da Zhou , Wen-Sen Li , Ling-Yi Kong , Ming-Hua Yang . Asperochones A and B, two antimicrobial aromatic polyketides from the endophytic fungus Aspergillus sp. MMC-2. Chinese Chemical Letters, 2024, 35(9): 109351-. doi: 10.1016/j.cclet.2023.109351
3. [3]
  Qi Tan , Run-Zhu Fan , Wencong Yang , Ge Zou , Tao Chen , Jianying Wu , Bo Wang , Sheng Yin , Zhigang She . (+)/(−)-Mycosphatide A, a pair of highly oxidized polyketides with lipid-lowering activity from the mangrove endophytic fungus Mycosphaerella sp. SYSU-DZG01. Chinese Chemical Letters, 2024, 35(9): 109390-. doi: 10.1016/j.cclet.2023.109390
4. [4]
  Yun-Feng Liu , Hui-Fang Du , Ya-Hui Zhang , Zhi-Qin Liu , Xiao-Qian Qi , Du-Qiang Luo , Fei Cao . Chaeglobol A, an unusual octocyclic sterol with antifungal activity from the marine-derived fungus Chaetomium globosum HBU-45. Chinese Chemical Letters, 2025, 36(3): 109858-. doi: 10.1016/j.cclet.2024.109858
5. [5]
  Xia Wei , Zheng-Wu Luo , Guo-Qiang Zhang , Yan-An Lin , Ze-Kun Zhang , Lin-Kun An , Xi-Xin He , Jun-Cheng Su , Cui-Xian Zhang . Sterpiperazines A and B, steroid-indole alkaloids with Tdp1 inhibitory and chemotherapy sensitizing activities from marine fungus Aspergillus sp. EGF 15-0-3. Chinese Chemical Letters, 2026, 37(2): 111048-. doi: 10.1016/j.cclet.2025.111048
6. [6]
  Bin Fang , Jiaqi Yang , Limin Wang , Haoqin Li , Jiaying Guo , Jiaxin Zhang , Qingyuan Guo , Bo Peng , Kedi Liu , Miaomiao Xi , Hua Bai , Li Fu , Lin Li . A mitochondria-targeted H₂S-activatable fluorogenic probe for tracking hepatic ischemia-reperfusion injury. Chinese Chemical Letters, 2024, 35(6): 108913-. doi: 10.1016/j.cclet.2023.108913
7. [7]
  Dong-Xue Jiao , Hui-Li Zhang , Chao He , Si-Yu Chen , Ke Wang , Xiao-Han Zhang , Li Wei , Qi Wei . Layered (C5H6ON)2[Sb2O(C2O4)3] with a large birefringence derived from the uniform arrangement of π-conjugated units. Chinese Journal of Structural Chemistry, 2024, 43(6): 100304-100304. doi: 10.1016/j.cjsc.2024.100304
8. [8]
  Wei Zhou , Xi Chen , Lin Lu , Xian-Rong Song , Mu-Jia Luo , Qiang Xiao . Recent advances in electrocatalytic generation of indole-derived radical cations and their applications in organic synthesis. Chinese Chemical Letters, 2024, 35(4): 108902-. doi: 10.1016/j.cclet.2023.108902
9. [9]
  Zheng-Biao Zou , Tai-Zong Wu , Chun-Lan Xie , Yuan Wang , Yan Li , Gang Zhang , Rong Chao , Lian-Zhong Luo , Li-Sheng Li , Xian-Wen Yang . neo-Dicitrinols A–C: Unprecedented PKS-NRPS hybrid citrinin dimers with ferroptosis inhibitory activity from the deep-sea-derived Penicillium citrinum W22. Chinese Chemical Letters, 2024, 35(12): 109723-. doi: 10.1016/j.cclet.2024.109723
10. [10]
  Chunlei Dai , Liying Wang , Xinru You , Yi Zhao , Zhong Cao , Jun Wu . Coffee-derived self-anti-inflammatory polymer as drug nanocarrier for enhanced rheumatoid arthritis treatment. Chinese Chemical Letters, 2025, 36(3): 109869-. doi: 10.1016/j.cclet.2024.109869
11. [11]
  Guo-Ping Yin , Ya-Juan Li , Li Zhang , Ling-Gao Zeng , Xue-Mei Liu , Chang-Hua Hu . Citrinsorbicillin A, a novel homotrimeric sorbicillinoid isolated by LC-MS-guided with cytotoxic activity from the fungus Trichoderma citrinoviride HT-9. Chinese Chemical Letters, 2024, 35(8): 109035-. doi: 10.1016/j.cclet.2023.109035
12. [12]
  Xiaodong Zhang , Bohui Xu , Deshuai Xiao , Xinyuan Zhang , Pifu Gong , Zheshuai Lin . From centrosymmetric CN3H6C6H5SO3 to non-centrosymmetric CN3H6C6H4SO3(OH): Hydroxyl introduced hydrogen bond reconstruction to realize strong second harmonic generation. Chinese Journal of Structural Chemistry, 2025, 44(10): 100707-100707. doi: 10.1016/j.cjsc.2025.100707
13. [13]
  Han Han , Bi-Te Chen , Jia-Rong Ding , Jin-Ming Si , Tian-Jiao Zhou , Yi Wang , Lei Xing , Hu-Lin Jiang . A PDGFRβ-targeting nanodrill system for pancreatic fibrosis therapy. Chinese Chemical Letters, 2024, 35(10): 109583-. doi: 10.1016/j.cclet.2024.109583
14. [14]
  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
15. [15]
  Xingyue Yuan , Li Wu , Qiuyu Peng , Yanyan Tang , Mingxu Wang , Yuhang Wei , Zhu Tao , Xin Xiao . Developing color-tunable long afterglow anti-counterfeiting materials using cucurbit[6]uril and classical aggregation-caused quenching compounds through multiple non-covalent interactions. Chinese Chemical Letters, 2025, 36(9): 110821-. doi: 10.1016/j.cclet.2025.110821
16. [16]
  Jinpeng Du , Junlin Chen , Yulong Shan , Tongliang Zhang , Yu Sun , Zhongqi Liu , Xiaoyan Shi , Wenpo Shan , Yunbo Yu , Hong He . Insight into the effects of C₃H₆ on fresh and hydrothermally aged Cu-SSZ-39 catalysts. Chinese Chemical Letters, 2025, 36(3): 110019-. doi: 10.1016/j.cclet.2024.110019
17. [17]
  Tong Zhang , Chao Sun , Shubin Yang , Zimin Cai , Sifeng Zhu , Wendian Liu , Yun Luan , Cheng Wang . Inhalation of taraxasterol loaded mixed micelles for the treatment of idiopathic pulmonary fibrosis. Chinese Chemical Letters, 2024, 35(8): 109248-. doi: 10.1016/j.cclet.2023.109248
18. [18]
  Yan Yu , Cailing Gan , Kun Shi , Zhongwu Bei , Yang Yu , Meng Pan , Hanzhi Deng , Zhiyong Qian . Recent advances in drug delivery systems for pulmonary fibrosis therapy. Chinese Chemical Letters, 2026, 37(1): 111596-. doi: 10.1016/j.cclet.2025.111596
19. [19]
  Yun-Hong Yu , Yu Peng , Wei-Dong Z. Li . Highly fused tetracyclic diterpenoid natural products: Diverse biosynthesis and total synthesis. Chinese Chemical Letters, 2025, 36(10): 111137-. doi: 10.1016/j.cclet.2025.111137
20. [20]
  Jiying Liu , Zehua Li , Wenjing Zhang , Donghui Wei . Molecular Orbital and Nucleus-Independent Chemical Shift Calculations for C₆H₆ and B₁₂H₁₂^2-: A Computational Chemistry Experiment. University Chemistry, 2025, 40(3): 186-192. doi: 10.12461/PKU.DXHX202406085

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