Synthesis and biological evaluation of novel demethylzeylasteral derivatives as potential anticancer agents

Xiaojing Sun, Lin Xing, Jieying Yuan, Enxiao Wang, Yuxin Ding, Ruilong Sheng, Fang Wang, Wenhui Wu, Xiuwei H. Yang, Ruihua Guo

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


Demethylzeylasteral (DEM), a class of terpenoids isolated from natural plants, frequently exhibits moderate or limited inhibitory effect on tumor growth across multiple cancer types. Thus, here we attempted to elevate the anti-tumor efficacy of DEM by altering active groups in its chemical structure. Initially, we synthesized a series of novel DEM derivatives 1–21 through performing a series of modifications of its phenolic hydroxyl groups at C-2/3, C-4 and C-29 positions. The anti-proliferative activities of these new compounds were subsequently assessed using three human cancer cell line models (A549, HCT116 and HeLa) and CCK-8 assay. Our data showed that compared to original DEM compound, derivative 7 exhibited remarkable inhibition effect on A549 (16.73 ± 1.07 μM), HCT116 (16.26 ± 1.94 μM) and HeLa (17.07 ± 1.09 μM), almost reaching to the same level of DOX. Moreover, the structure-activity relationships (SARs) of the synthesized DEM derivatives were discussed in detail. We found that treatment with derivative 7 only led to moderate cell cycle arrest at S-phase in a concentration-dependent manner. Meanwhile, derivative 7 treatment markedly induced apoptosis in tumor cells. Consistent with this observation, our subsequent docking analysis showed that derivative 7 is capable of activating caspase-3 through interaction with the His 121 and Gly 122 residues of the enzyme. Overall, we have developed a new series of DEM derivatives with elevated anti-tumor efficacy relative to its parent form. The results suggested that derivative 7 has great potential to be employed as an anticancer agent candidate for natural product-based cancer chemotherapy.

Original languageEnglish
Article number105504
StatePublished - Jun 2023

Bibliographical note

Publisher Copyright:
© 2023 Elsevier B.V.


  • Anticancer activity
  • Demethylzeylasteral
  • Derivative
  • Lung cancer
  • Molecular docking
  • Structure activity relationships

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery


Dive into the research topics of 'Synthesis and biological evaluation of novel demethylzeylasteral derivatives as potential anticancer agents'. Together they form a unique fingerprint.

Cite this