Chuanzhu Gao

Host–guest inclusion system of mangiferin with β-cyclodextrin and its derivatives

The characterization, inclusion complexation behavior and binding ability of the inclusion complexes of mangiferin (MGF) with β-cyclodextrin and its derivatives (hydroxypropyl-β-cyclodextrin (HPβCD), sulfobutyl ether β-cyclodextrin (SBEβCD) and mono (6-ethylene-diamino-6-deoxy)-β-cyclodextrin (ENβCD)) were investigated in both solution and solid state by means of PL spectroscopy, (1)H and 2D NMR, XRD, TG and DSC. The results showed that the water solubility and thermal stability of MGF were significantly increased in the inclusion complex with cyclodextrins. The MGF/CDs complexes will be potentially useful for the design of a novel formulation of mangiferin for herbal medicine.

Scutellarin-cyclodextrin conjugates: synthesis, characterization and anticancer activity.

A series of scutellarin-cyclodextrin conjugates (SCU-CD conjugates), in which scutellarin was covalently bound to one of the primary hydroxyl groups of β-CD, were prepared, and their structures were determined using NMR and MS. These conjugates were further characterized by XRD and TG. The results showed that the aqueous solubility of the conjugates was much higher than that of scutellarin, and the conjugates could hardly be hydrolyzed to scutellarin in aqueous solutions. The cytotoxicity of SCU-CD conjugates on human colon cancer cell lines HT-29, SW480, Lovo and HTC116 indicated that the antitumor activities of the conjugates were better than that of scutellarin. This high antitumor activity, along with the satisfactory aqueous solubility and high stability of the conjugates, will be potentially useful for their application on human colon cancer chemotherapies.

A novel polyrotaxane-based delivery system for scutellarin: preparation, characterization, and in vitro evaluation

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.

Host-guest inclusion system of scutellarein with 2-hydroxypropyl-beta-cyclodextrin: preparation, characterization, and anticancer activity

The inclusion complexation behavior of scutellarein (SCUE) with 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) has been investigated in both solution and in the solid state. SCUE/HP-β-CD solid system was prepared by suspension method. The formation of SCUE/HP-β-CD complex in aqueous solution was demonstrated by fluorescence spectroscopy, and the Job plot showed a maximum at a molar fraction of 0.5, indicating 1:1 inclusion complexation between SCUE and HP-β-CD. However, SCUE/HP-β-CD inclusion complex was characterized by means of XRD, DSC, 1H, and two-dimensional NMR. Through the complexation between HP-β-CD and SCUE, the water solubility and antitumor activity of SCUE were obviously increased. This satisfactory water solubility and high antitumor activity of the SCUE/HP-β-CD complex will be potentially useful for its application on human colon cancer chemotherapies.

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

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.

Targeted Drug Delivery System for Platinum-based Anticancer Drugs

Platinum-based (Pt-based) anticancer drugs have been recognised as one of the most effective drugs for clinical treatment of malignant tumors due to its unique mechanism of action and broad range of anticancer spectrum. But, there are still some limitations such as side effects, drug resistance/cross resistance, no-specific targeting, becoming obstacles to restrict its expanding of clinical application. Targeted drug delivery system (TDDS) is a promising strategy for the research of novel Pt-based anticancer drugs. A variety of TDDS have been explored to improve the antitumor activity of Pt-based drugs such as nanoparticle drug systems, polymer-drug systems, drugs-macrocyclic compounds systems, etc. The review concentrates on recent development of various targeted drug delivery techniques, which could provide more opportunities for the development of Pt-based drugs with better efficiency, lower toxicity and less resistance.

Preparation and in vitro cytotoxicity of oxaliplatin derivatives with chiral amino acid as the carrier group

Eight oxaliplatin derivatives with chiral amino acid, 2-{[(1R,2R)-2-aminocyclohexyl]amino}propanoic acid, as the carrier group, were designed, synthesized, and spectrally characterized by IR, 1H NMR, MS spectra, and microanalyses. In vitro cytotoxicities against human HepG-2, MCF-7, A549, and HCT-116 cell lines were evaluated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazo-liumbromide assay. Results indicated that all compounds exhibited sensitivity to HepG-2 cell line, and among them, compounds P3 and P4 which have CH3(CH2)6COO– and CH3(CH2)8COO– as the leaving groups, respectively, gave better antitumor activity than carboplatin against HepG-2 and A549 cell lines. Graphical Abstract Novel platinum(II) compounds with a new chiral ligand were designed, prepared and biologically evaluated. Results indicated that compounds P3 and P4 showed better antitumor activity than carboplatin against two selected human cell lines.

Synthesis and in vitro cytotoxicity of platinum(II) complexes with chiral N-monosubstituted 1,2-cyclohexyldiamine derivatives as the carrier groups

Eight platinum(II) complexes with the new chiral ligands, (1R,2R)-N 1-(pyridine-2-ylmethyl) cyclohexane-1,2-diamine (R) or (1S,2S)-N 1-(pyridine-2-ylmethyl) cyclohexane-1,2-diamine (S) as the carrier groups were designed, synthesized, and spectrally characterized. All platinum(II) complexes showed much better aqueous solubility than cisplatin and oxaliplatin. In vitro cytotoxicity of the compounds against human HepG-2, MCF-7, A549, and HCT-116 cell lines was evaluated. Results indicate that all compounds with R as the carrier group showed cytotoxicity against HCT-116, A549, and MCF-7 cell lines; however, all compounds with S as carrier group exhibited disappointing cytotoxicity against tested cell lines. Compound R2, bearing ClCH2COO- as leaving group, exhibited better cytotoxicity than that of carboplatin against A549 and MCF-7 cell lines and also showed close activity to oxaliplatin against HCT-116 cell line.

Host-guest inclusion system of norathyriol with β-cyclodextrin and its derivatives: preparation, characterization, and anticancer activity.

The characterization, binding ability and inclusion complexation behavior of the inclusion complexes of norathyriol with β-cyclodextrin (β-CD) and its derivatives such as hydroxypropyl-β-cyclodextrin (HPβCD), sulfobutyl ether β-cyclodextrin (SBEβCD) and mono (6-ethylene-diamino-6-deoxy)-β-cyclodextrin (ENβCD) were investigated in both solution and solid state by means of femtosecond spectroscopy, (1)H and 2D nuclear magnetic resonance, powder X-ray diffraction. The results showed that the aqueous solubility of the complexes was much higher than that of norathyriol. The cytotoxicity of complexes on human colon cancer cell lines HT-29, SW480, Lovo and HCT116 indicated that the antitumor activities of the complexes were better than that of norathyriol. This high antitumor activity, along with the satisfactory aqueous solubility of the complexes, will be potentially useful for their application on cancer chemotherapies.

Synthesis, characterization and in vitro evaluation of a series of novel polyrotaxane-based delivery system for artesunate

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.