Synthesis, characterization, and in vitro evaluation of artesunate-β-cyclodextrin conjugates as novel anti-cancer prodrugs

Carbohydr Res. 2014 Dec 5:400:19-25. doi: 10.1016/j.carres.2014.08.018. Epub 2014 Sep 8.

Abstract

A novel series of artesunate-β-cyclodextrin (ATS-β-CD) conjugates, in which artesunate (ATS) was coupled covalently to one of the primary hydroxyl groups of β-cyclodextrin (β-CD) through amino bond formation, were synthesized and characterized by (1)H NMR, HRMS, 2D NMR (ROESY), X-ray diffraction (XRD), and thermogravimetric analysis (TGA). The results showed that the aqueous solubility of ATS-β-CD conjugates was 26-45 times better than that of free ATS. The cytotoxicity of the ATS-β-CD conjugates was evaluated on human colon cancer cell lines HCT116, LOVO, SW480, and HT-29, and the results indicated that ATS-2NβCD exhibited a very high cytotoxicity against HCT116, LOVO, and HT-29 with IC50 values of 0.58, 1.62, and 5.18μmol/L, respectively. In addition, the supposition of better cytotoxicity was further supported by the control experiment of fluorescent cyclodextrin.

Keywords: Anti-cancer; Artesunate; Carrier; Conjugate; Prodrug; β-Cyclodextrin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Artemisinins / administration & dosage*
  • Artemisinins / chemical synthesis
  • Artemisinins / chemistry
  • Artesunate
  • Cell Proliferation / drug effects*
  • Cyclodextrins / administration & dosage*
  • Cyclodextrins / chemical synthesis
  • Cyclodextrins / chemistry
  • HCT116 Cells
  • HT29 Cells
  • Humans
  • In Vitro Techniques
  • Magnetic Resonance Spectroscopy
  • Prodrugs / administration & dosage*
  • Prodrugs / chemical synthesis
  • Prodrugs / chemistry
  • Solubility / drug effects
  • X-Ray Diffraction

Substances

  • Artemisinins
  • Cyclodextrins
  • Prodrugs
  • Artesunate