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

A novel series of artesunate-beta-cyclodextrin (ATS-beta-CD) conjugates, in which artesunate (ATS) was coupled covalently to one of the primary hydroxyl groups of beta-cyclodextrin (beta-CD) through amino bond formation, were synthesized and characterized by H-1 NMR, HRMS, D-2 NMR (ROESY), X-ray diffraction (XRD), and thermogravimetric analysis (TGA). The results showed that the aqueous solubility of ATS-beta-CD conjugates was 26-45 times better than that of free ATS. The cytotoxicity of the ATS-beta-CD conjugates was evaluated on human colon cancer cell lines HCT116, LOVO, SW480, and HT-29, and the results indicated that ATS-2N beta CD exhibited a very high cytotoxicity against HCT116, LOVO, and HT-29 with IC50 values of 0.58, 1.62, and 5.18 mu mol/L, respectively. In addition, the supposition of better cytotoxicity was further supported by the control experiment of fluorescent cyclodextrin. (C) 2014 Elsevier Ltd. All rights reserved.