Bingquan Wang

Inclusion complexes of quercetin with three β-cyclodextrins derivatives at physiological pH: Spectroscopic study and antioxidant activity

Properties of the inclusion complexes of quercetin (QUE) with sulfobutyl ether-β-cyclodextrin (SBE-β-CD), hydroxypropyl-β-cyclodextrin (HP-β-CD), and methylated-β-cyclodextrin (M-β-CD) in tris-HCl buffer solutions of pH 7.40 were investigated. The stoichiometry and thermodynamic parameters for the complexation process (stability constants K, Gibbs free energy change ΔG, enthalpy change ΔH and entropy change ΔS) were determined using phase-solubility and fluorescence spectra analysis. The thermodynamic studies indicated that the inclusion reactions between QUE and the three β-CDs are enthalpy-driven processes. Proton nuclear magnetic resonance spectroscopy indicated that B-ring, C-ring, and part of A-ring of QUE interact with the cavity of β-CDs. The antioxidant activity of QUE and its inclusion complexes were determined by the scavenging of stable radical DPPH(*). The results showed that the complexed QUE/CDs were more effective than free QUE, with the QUE/SBE-β-CD complex as the best form.

Competitive binding of (−)-epigallocatechin-3-gallate and 5-fluorouracil to human serum albumin: A fluorescence and circular dichroism study

Combination therapy with more than one therapeutic agent can improve therapeutic efficiency and decrease drug resistance. In this study, the interactions of human serum albumin (HSA) with individual or combined anticancer drugs, (-)-epigallocatechin-3-gallate (EGCG) and 5-fluorouracil (FU), were investigated by fluorescence and circular dichroism (CD) spectroscopy. The results demonstrated that the interaction of EGCG or FU with HSA is a process of static quenching and EGCG formed a more stable complex. The competitive experiments of site markers suggested that both anti-carcinogens mainly bound to site I (subdomain IIA). The interaction forces which play important roles in the binding process were discussed based on enthalpy and entropy changes. Moreover, the competition binding model for a ternary system was proposed so as to precisely calculate the binding parameters. The results demonstrated that one drug decreased the binding affinity of another drug with HSA, resulting in the increasing free drug concentration at the action sites. CD studies indicated that there was an alteration in HSA secondary structure due to the binding of EGCG and FU. It can be concluded that the combination of EGCG with FU may enhance anticancer efficacy. This finding may provide a theoretical basis for clinical treatments.

Improved stability of (+)-catechin and (-)-epicatechin by complexing with hydroxypropyl-β-cyclodextrin: Effect of pH, temperature and configuration.

The stability and bioavailability of catechins, a kind of tea polyphenols with health benefit, could be improved by complexing with cyclodextrins. The aim of this study was to investigate the complexation of two geometrical isomers, (+)-catechin and (-)-epicatechin, with hydroxypropyl-β-cyclodextrin (HP-β-CD) in tris-HCl buffer solutions at pH 6.8-8.0 using isothermal titration calorimetry, fluorescence and proton nuclear magnetic resonance spectroscopy. Experimental results showed that these inclusion interactions are primarily enthalpy-driven processes. The complexation constant (KC) of EC+HP-β-CD complex was less than that of CA+HP-β-CD at the same temperature and pH value. Temperature and pH studies showed that the KC value decreased with the rise of temperature and pH. Stability study indicated that HP-β-CD showed a stronger protection effect on CA than that on EC. The different inclusion modes between CA and EC were discussed in terms of the discrepancy in their molecular structures.

Poly(glutamic acid) hydrogels crosslinked via native chemical ligation

Mild crosslinking methods, which have a strong influence on biomedical hydrogels and scaffolds, have attracted wide attention in recent years. In this project, native chemical ligation (NCL) was utilized to prepare biocompatible and biodegradable hydrogels using naturally derived poly(glutamic acid) (PGA) with no additives or by-products. Firstly, thiolactone-grafted poly(glutamic acid) (PGA-HC) and cysteine-grafted poly(glutamic acid) (PGA-C) precursors were synthesized. Their structure was confirmed by nuclear magnetic resonance (NMR). Then, hydrogels crosslinked by NCL were formed by blending buffered solutions of PGA-HC and PGA-C with no additives under physiological conditions. After that, the equilibrium water content, morphology, degradation rate and mechanical properties of the hydrogels were characterized in detail. The data showed that the PGA hydrogels had gelation times, water contents and mechanical properties that were tunable by adjusting the precursor composition. Furthermore, the biocompatibility of the hydrogels was confirmed by an MTT assay. These characteristics provide a potential opportunity for the NCL hydrogels as wound dressings, skin fillings, drug delivery vehicles and tissue regeneration matrices.

Design and synthesis of a new series of low toxic naphthalimide platinum(IV) antitumor complexes with dual DNA damage mechanism

ABSTRACT Naphthalimide platinum(IV) antitumor complexes with potential dual DNA damage mechanism were designed, synthesized and evaluated for antitumor activities. The incorporation of DNA targeted naphthalimide group to the platinum(IV) system exerts much positive impacts on their antitumor efficacy. The mechanism research reveals that the title compounds could interact with dsDNA in platinum(IV) form via the naphthalimide group and cause DNA lesion. The further reduction would release platinum(II) complexes and naphthalimide acids which would induce remarkable secondary damage to DNA. Furthermore, the naphthalimide platinum(IV) compounds could combine with human serum albumin via electrostatic force, which are favourable for their storage and transport in blood. Moreover, the title compounds exhibit higher accumulation in tumor cells, and exert lower toxic and higher safe properties than oxaliplatin in vivo.