Citation: 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[J]. Chinese Chemical Letters, ;2026, 37(2): 111048. doi: 10.1016/j.cclet.2025.111048 shu

Sterpiperazines A and B, steroid-indole alkaloids with Tdp1 inhibitory and chemotherapy sensitizing activities from marine fungus Aspergillus sp. EGF 15-0-3

Xia Wei ^{a, b, c, 1} ,
Zheng-Wu Luo ^{a, 1} ,
Guo-Qiang Zhang ^a ,
Yan-An Lin ^a ,
Ze-Kun Zhang ^a ,
Lin-Kun An ^d ,
Xi-Xin He ^a ,
Jun-Cheng Su ^{c, *,} ,
Cui-Xian Zhang ^{a, *,}

a.
School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China
b.
Guangxi Key Laboratory of Bioactive Molecules Research and Evaluation, School of Pharmaceutical Sciences, Guangxi Medical University, Nanning 530021, China
c.
Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Ministry of Education of China), Guangxi Key Laboratory of Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin 541004, China
d.
School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China

su_juncheng@163.com

zhangcuixian@gzucm.edu.cn

Received Date: 27 December 2024
Revised Date: 4 March 2025
Accepted Date: 6 March 2025
Available Online: 7 March 2025

Figures(6)

Hyperactivation of DNA repairing pathway is highly associated with the chemosensitivity and chemoresistance of cancer cells. In this manuscript, guided by cascaded one strain many compounds-global natural products social molecular networking (OSMAC-GNPS) strategy, a pair of epimeric environmental-induced metabolites were isolated from Aspergillus sp. EGF 15-0-3. Structurally, sterpiperazines A (1) and B (2) represent the first steroid-based indole alkaloids with unprecedented backbones. Biologically, compound 1 could be identified as a novel tyrosyl-DNA phosphodiesterase 1 (Tdp1) inhibitor with a unique mechanism distinct from the reported modulators, and was able to significantly enhance the sensitivity of NCI-H460 cells to the clinic chemotherapeutic drug through inhibiting the DNA repairment and enhanced the DNA damage of cancer cells.
- Environmental-induced metabolites,
- Steroid-based indole alkaloids,
- Tdp1 inhibition,
- Chemotherapy sensitizing activities,
- Aspergillus sp. EGF 15-0-3
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