Design, synthesis and biological evaluation of novel α-hederagenin derivatives with anticancer activity

Xian xuan Liu, Yan ting Yang, Xiao Wang, Kai yi Wang, Jia qi Liu, Lei Lei, Xiao min Luo, Rong G Zhai, Feng hua Fu, Hong bo Wang, Yi Bi

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

In an attempt to arrive at a more potent cytotoxic agent than the parent compound α-hederagenin (H), 24 α-hederagenin derivatives (5–8, 11–24, 27–28, 31–32, and 35–36) were synthesized in a concise and efficient strategy and screened for in vitro cytotoxicity against the human cancer cell lines MKN45 and KB. Among these compounds, the polyamine derivative 15 exhibited more potency than the parent compound with IC50 values in the range of 4.22 μM–8.05 μM. Compound 15 increased Bax/bcl-2 ratio that disrupted the mitochondrial potential and induced apoptosis. Therefore, the present studies highlight the importance of polyamine derivatives of α-hederagenin in the discovery and development of novel anticancer agents.

Original languageEnglish (US)
Pages (from-to)427-439
Number of pages13
JournalEuropean Journal of Medicinal Chemistry
Volume141
DOIs
StatePublished - Dec 1 2017
Externally publishedYes

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Keywords

  • Apoptosis
  • Cancer
  • Synthesis
  • α-Hederagenin derivatives

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

Cite this

Liu, X. X., Yang, Y. T., Wang, X., Wang, K. Y., Liu, J. Q., Lei, L., Luo, X. M., Zhai, R. G., Fu, F. H., Wang, H. B., & Bi, Y. (2017). Design, synthesis and biological evaluation of novel α-hederagenin derivatives with anticancer activity. European Journal of Medicinal Chemistry, 141, 427-439. https://doi.org/10.1016/j.ejmech.2017.09.016