Synthesis and biological evaluation of novel H6 analogues as drug resistance reversal agents

Xiao Wang, Qian wen Ren, Xian xuan Liu, Yan ting Yang, Bing hua Wang, Rong Zhai, Jia Grace Qi, Jing wei Tian, Hong bo Wang, Yi Bi

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


Hederagenin is a naturally occurring pentacyclic triterpenoids compound with multiple pharmacological activities. We recently showed that H6, a synthetic derivative of hederagenin, could enhance the anticancer activity of paclitaxel in drug-resistant cells in vitro and in vivo, but showed poor solubility. With the aim of improving the drug resistant reversal activity of H6, here we designed and synthesized a series of novel H6 analogues. Our results showed that compound 10 at the concentration of 5 μM significantly enhanced the cytotoxicity of paclitaxel to drug-resistant KBV cells and sensitized cells to paclitaxel in arresting cells in G2/M phase and inducing apoptosis. We found that compound 10 might block the drug efflux of P-gp via stimulating P-gp ATPase activity. Importantly, compound 10 enhanced the efficacy of paclitaxel against KBV cancer cell-derived xenograft tumors. Finally, we summarized a preliminary structure-activity relationship of hederagenin by the drug resistant reversal activity of H6 analogues in vitro and compound 10 and H6 in vivo. This study highlights the importance of nitrogen-containing derivatives of hederagenin C-28 in the development of novel drug resistance reversal agents.

Original languageEnglish (US)
Pages (from-to)364-377
Number of pages14
JournalEuropean Journal of Medicinal Chemistry
StatePublished - Jan 1 2019
Externally publishedYes


  • Drug resistance reverse activity
  • H6 analogues
  • P-glycoprotein
  • Synthesis

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry


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