ABSTRACT
A series of novel artesunate-polyrotaxanes (ATS-PRs) with folic acid capped, in which artesunate (ATS) was covalently bound to a cyclodextrin (CD) of the polyrotaxane (PR), were synthesized and were characterized by NMR, XRD, TG and DSC. The cytotoxicities of ATS-PRs on human colon cancer cell lines HT-29, SW480, HTC116 and DLD-1 showed that their antitumor activities were better than that of artesunate (ATS) and dihydroartemisinin (DHA). These ATS-PRs may provide a useful approach to the development of a highly effective drug candidate for the chemotherapy of human colon cancer.
Subject(s)
Artemisinins/administration & dosage , Cyclodextrins/chemistry , Cyclodextrins/chemical synthesis , Drug Delivery Systems , Drug Evaluation , Poloxamer/chemistry , Poloxamer/chemical synthesis , Rotaxanes/chemistry , Rotaxanes/chemical synthesis , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Antineoplastic Agents/toxicity , Artemisinins/chemical synthesis , Artemisinins/toxicity , Artesunate , Calorimetry, Differential Scanning , Cell Line, Tumor , Colonic Neoplasms/metabolism , Cyclodextrins/toxicity , Humans , Magnetic Resonance Imaging , Poloxamer/toxicity , Rotaxanes/toxicity , X-Ray DiffractionABSTRACT
A novel series of artesunate-ß-cyclodextrin (ATS-ß-CD) conjugates, in which artesunate (ATS) was coupled covalently to one of the primary hydroxyl groups of ß-cyclodextrin (ß-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-ß-CD conjugates was 26-45 times better than that of free ATS. The cytotoxicity of the ATS-ß-CD conjugates was evaluated on human colon cancer cell lines HCT116, LOVO, SW480, and HT-29, and the results indicated that ATS-2NßCD 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.
Subject(s)
Artemisinins/administration & dosage , Cell Proliferation/drug effects , Cyclodextrins/administration & dosage , Prodrugs/administration & dosage , Artemisinins/chemical synthesis , Artemisinins/chemistry , Artesunate , Cyclodextrins/chemical synthesis , Cyclodextrins/chemistry , HCT116 Cells , HT29 Cells , Humans , In Vitro Techniques , Magnetic Resonance Spectroscopy , Prodrugs/chemical synthesis , Prodrugs/chemistry , Solubility/drug effects , X-Ray DiffractionABSTRACT
The safe and effective polyrotaxane-based drug delivery system could potentially increase the antiproliferative activity of antitumor medicine. A novel scutellarin-polyrotaxane (SCU-PR), in which scutellarin (SCU) was covalently bound to one of the hydroxyl groups of polyrotaxane (PR), was synthesized, and its characterization was further investigated by NMR, XRD, TG, DSC. The cytotoxicity of SCU-PR was assessed in vitro using human HCT116 and LOVO cell lines in results that the IC50 values of SCU-PR (1.03×10(-6) and 1.01×10(-6)mol/L, respectively), which compared with those of free SCU (7.80×10(-5) and 7.70×10(-5)mol/L, respectively), were lower. The valuable properties of SCU-PR will be potentially useful for its application on human colon cancer chemotherapies.
