Synthesis and biological evaluation of a novel artesunate-podophyllotoxin conjugate as anticancer agent

  • Bioorg Med Chem Lett. 2016 Jan 1;26(1):38-42. doi: 10.1016/j.bmcl.2015.11.042.
Lei Zhang  1 ,  Fan Chen  2 ,  Zeguo Zhang  2 ,  Yongzheng Chen  2 ,  Jing Wang  3
Affiliations
  • 1. School of Pharmacy, Zunyi Medical University, 201 Dalian Road, Zunyi 563003, PR China. Electronic address: [email protected].
  • 2. School of Pharmacy, Zunyi Medical University, 201 Dalian Road, Zunyi 563003, PR China.
  • 3. School of Pharmacy, Zunyi Medical University, 201 Dalian Road, Zunyi 563003, PR China. Electronic address: [email protected].
PMID: 26615886 DOI: 10.1016/j.bmcl.2015.11.042
Abstract

A novel conjugate of artesunate-podophyllotoxin was prepared and evaluated for its cytotoxicity against diverse normal and multidrug resistance human Cancer cell lines by CCK-8 assay. The conjugate exhibited good cytotoxicity on all the cell lines with IC50 values of 0.453±0.156-3.011±0.272μM and reduced the resistant factor. The conjugate was further found to disrupt the microtubule network and induce G2/M cell cycle arrest in multidrug resistance K562/ADR cells. Meanwhile, Hoechst staining analysis suggested that conjugate induced cell death by Apoptosis. Furthermore, conjugate could downregulate the levels of P-glycoprotein (P-gp) in P-gp overexpressing K562/ADR cells.

Keywords
Apoptosis; Artesunate; Cell cycle; Cytotoxicity; Microtubule; Podophyllotoxin.