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

•Four artesunate-β-cyclodextrin conjugates were prepared and confirmed.•XRD and TG spectrometry characterized these conjugates.•The aqueous solubility of the conjugates was much higher than that of artesunate.•The anti-colon cancer activities of ATS-2NβCD were better than those of artesunate.•The me...

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Bibliographic Details
Published in:Carbohydrate research 2014-12, Vol.400, p.19-25
Main Authors: Jiang, Rui-jian, Zhao, Yu-lin, Chen, Yun-jian, Xiao, Dan, Wang, Fen, Han, Bin, Yang, Jian, Liao, Xia-li, Yang, Li-Juan, Gao, Chuan-zhu, Yang, Bo
Format: Article
Language:English
Subjects:
Anti-cancer
Artemisinins - administration & dosage
Artemisinins - chemical synthesis
Artemisinins - chemistry
Artesunate
Carrier
Cell Proliferation - drug effects
Conjugate
Cyclodextrins - administration & dosage
Cyclodextrins - chemical synthesis
Cyclodextrins - chemistry
HCT116 Cells
HT29 Cells
Humans
In Vitro Techniques
Magnetic Resonance Spectroscopy
Prodrug
Prodrugs - administration & dosage
Prodrugs - chemical synthesis
Prodrugs - chemistry
Solubility - drug effects
X-Ray Diffraction
β-Cyclodextrin
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Summary:•Four artesunate-β-cyclodextrin conjugates were prepared and confirmed.•XRD and TG spectrometry characterized these conjugates.•The aqueous solubility of the conjugates was much higher than that of artesunate.•The anti-colon cancer activities of ATS-2NβCD were better than those of artesunate.•The mechanism of conjugates to release free drug into the cancer cells was explored. 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 1H 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.
ISSN:0008-6215
1873-426X
DOI:10.1016/j.carres.2014.08.018