2. Academic Validation
  3. Bioactive sesquiterpene lactones from Elephantopus scaber: semi-synthesis, target fishing, anti-malignant glioma efficacy in vitro and in vivo

Bioactive sesquiterpene lactones from Elephantopus scaber: semi-synthesis, target fishing, anti-malignant glioma efficacy in vitro and in vivo

  • Eur J Med Chem. 2025 Nov 5:297:117954. doi: 10.1016/j.ejmech.2025.117954.
Hui Ren 1,  Kun Tao 2,  Jun Liu 3,  Lin Zu 2,  Yuyang Liu 1,  Yaodong Hu 3,  Bensong Xin 1,  Li Ye 1,  Ming Bai 1,  Guo-Dong Yao 1,  Qingbo Liu 4,  Wei Cui 5,  Shao-Jiang Song 6
Affiliations

Affiliations

  • 1 Key Laboratory of Computational Chemistry-Based Natural Antitumor Drug Research & Development, Liaoning, Shenyang Pharmaceutical University, Shenyang 110016, China; School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China; Engineering Research Center of Natural Medicine Active Molecule Research & Development, Liaoning, Shenyang Pharmaceutical University, Shenyang 110016, China; Key Laboratory of Natural Bioactive Compounds Discovery & Modification, Shenyang, Shenyang Pharmaceutical University, Shenyang 110016, China.
  • 2 Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang, China.
  • 3 Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, China.
  • 4 Key Laboratory of Computational Chemistry-Based Natural Antitumor Drug Research & Development, Liaoning, Shenyang Pharmaceutical University, Shenyang 110016, China; School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China; Engineering Research Center of Natural Medicine Active Molecule Research & Development, Liaoning, Shenyang Pharmaceutical University, Shenyang 110016, China; Key Laboratory of Natural Bioactive Compounds Discovery & Modification, Shenyang, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address: liuqingbolily@163.com.
  • 5 Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang, China. Electronic address: cuiwei@syphu.edu.cn.
  • 6 Key Laboratory of Computational Chemistry-Based Natural Antitumor Drug Research & Development, Liaoning, Shenyang Pharmaceutical University, Shenyang 110016, China; School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China; Engineering Research Center of Natural Medicine Active Molecule Research & Development, Liaoning, Shenyang Pharmaceutical University, Shenyang 110016, China; Key Laboratory of Natural Bioactive Compounds Discovery & Modification, Shenyang, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address: songsj99@163.com.
PMID: 40680455 DOI: 10.1016/j.ejmech.2025.117954
Abstract

Traditional Chinese Medicine (TCM) offers distinct advantages in the treatment of tumors, since it serves dually as both a medicinal treatment and a dietary therapy. Elephantopus scaber (E. scaber), with a plethora of folk medicinal usage for treating pneumonia and hepatitis, contains sesquiterpene lactone (SL) as the primary component for therapeutic efficacy. The orphan drug ACT001, as the SL derivative, has been used in the treatment of glioma, which demonstrated significant potential for the development of such compounds. In this work, two series of plant-derived SL derivatives were synthesized and their efficacy against malignant glioma (MG) was evaluated. Among them, compound 1e exhibited the most potent inhibitory effects with IC50 values of 3.95 and 3.43 μM against U87 and T98G cells, respectively. Preliminary mechanism investigations suggested that 1e induced the cell-cycle arrest at S phase and inhibited the tube formation to the anti-angiogenesis. Meanwhile, 1e enhanced E-cadherin protein level while decreased the levels of Vimentin, MMP-2 and MMP9, thereby suppressing MG cells migration and invasion. Furthermore, the orthotopic glioma model using live animal fluorescence imaging demonstrated the therapeutic effect of 1e on MG in vivo and pharmacokinetic studies indicated 1e with a favorable pharmacokinetic profile. Moreover, we performed competitive activity-based protein profiling (ABPP) to explore the potential targets of SL derivatives in U87 cells, providing a basis for the follow-up studies of MG.

Keywords

ABPP; Anti-glioma efficacy; Elephantopus scaber; Sesquiterpene lactone.

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