2. Academic Validation
  3. Semisynthesis and Non-Small-Cell Lung Cancer Cytotoxicity Evaluation of Germacrane-Type Sesquiterpene Lactones from Elephantopus scaber

Semisynthesis and Non-Small-Cell Lung Cancer Cytotoxicity Evaluation of Germacrane-Type Sesquiterpene Lactones from Elephantopus scaber

  • J Nat Prod. 2022 Feb 25;85(2):352-364. doi: 10.1021/acs.jnatprod.1c00936.
Hui Ren 1,  Yang-Yang Zhang 1,  Ya-Ling Li 1,  Ming Bai 1,  Qiu-Lin Yan 1,  Xiao-Xiao Huang 1,  Wei Cui 2,  Hongwei Zhao 3,  Liwei Gu 4,  Qingbo Liu 1 3,  Guo-Dong Yao 1,  Shao-Jiang Song 1
Affiliations

Affiliations

  • 1 Key Laboratory of Computational Chemistry Based Natural Antitumor Drug Research & Development, Liaoning Province, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China.
  • 2 School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China.
  • 3 Jilin Yizheng Pharmaceutical Group Co., Ltd., Siping 136001, Jilin Province, People's Republic of China.
  • 4 Institute of Chinese Materia Medica, Artemisinin Research Center, China Academy of Chinese Medical Sciences, Beijing 100700, People's Republic of China.
PMID: 35090346 DOI: 10.1021/acs.jnatprod.1c00936
Abstract

Two series of germacrane-type sesquiterpene lactones were produced by semisynthetic modulation of scaberol C, which was prepared by a standard chemical transformation from an Elephantopus scaber extract. Their inhibition activities against non-small-cell lung Cancer cells were screened, and preliminary structure-activity relationships were also established. Among them, monomeric analog 1u and dimeric analog 3d exhibited superior anti-non-small-cell lung Cancer cytotoxic potencies with IC50 values of 4.3 and 0.7 μM against A549 cells, respectively, and were more active than cisplatin and the standard sesquiterpene lactones, parthenolide and scabertopin. Further studies revealed that compounds 1u and 3d cause G2/M phase arrest and induce Apoptosis through the activation of mitochondrial pathways in A549 cells. Collectively, the results obtained suggest that compounds 1u and 3d are promising anti-non-small-cell lung Cancer lead compounds.

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