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20(S)-protopanaxatriol (PPT) is a kind of tetracyclic triterpenoid, which is found in the roots of ginseng. It is well known as a potential herbal medicine or healthcare product. However, given its poor water solubility, its application has been limited. In this study, we successfully synthesized a novel mono-[6-(N,N-bis(3-aminopropyl)ethylenediamine)-6-deoxy]-β-cyclodextrin. We prepared inclusion complexes of PPT with three polyamine-modified β-cyclodextrins (CDs) (H1, H2, and H3) of different lengths by the coprecipitation method, aiming at enhancing the aqueous solubility of PPT. The host–guest inclusion complexes of H1, H2, and H3 with PPT were characterized via 1H NMR, XRD, FT-IR spectra, and SEM technology, and the inclusion modes were analyzed by 2D ROESY. The stability constant (Ks), inclusion ratios, and solubility of H1, H2, and H3 with PPT were determined via the phase solubility method. The stability constants (K1:1) were found to be 182.6, 94.2, and 524.4 M−1 for H1/PPT, H2/PPT, and H3/PPT inclusion complexes, with AL-, AN-, and BS-type curves, respectively. That is, when the stoichiometric ratio was 1:1, H3 (with longest-length chain) displayed the strongest binding ability with PPT. The host–guest size/shape-fit relationship and hydrogen bond interaction play a role in improving the stability of H1/PPT, H2/PPT, and H3/PPT inclusion complexes. Through complexation with H1, H2, and H3, the apparent solubility of PPT was obviously increased from the initial value of 0.062 mg/L to 5.1, 3.0, and 7.5 g/L, respectively. Among the three CDs, the solubilization effect of PPT with H3 was the best. Furthermore, H1/PPT, H2/PPT, and H3/PPT inclusion complexes exhibited some activity in inhibiting LPS-induced nitric oxide (NO) generation in macrophages. This satisfactory aqueous solubility and higher stability of H1/PPT, H2/PPT, and H3/PPT inclusion complexes should be possibly useful for its utilization as a herbal medicine and healthcare product. [ABSTRACT FROM AUTHOR]

Celastrol (CSL), the major constituent from traditional Chinese medicine Tripterygium wilfordii Hook, has attracted considerable interest in the medicinal society due to its multiple biological activities. However, poor solubility and obvious toxic side effect have limited its application in the pharmaceutical field. To address the problems, the inclusion complexes of mono polyamine-modified β-CD (H1) and the polyamine-brideged bis(β-CD) (H2) with CSL were prepared. The characterization of inclusion complexes was investigated by NMR, XRD FT-IR and SEM, and the binding behaviors of H1-2 with CSL were investigated by UV. The results showed that the H2 gave the binding constant (Ks) towards CSL up to 1.7 times higher than that of H1, through cooperative binding of two hydrophobic CD cavities with one guest. Remarkably, complexation with H1 and H2 improved CSL solubility in water from 0.044 mg/mL up to 2.31 and 2.68 mg/mL, respectively. The in vitro anticancer activity of H1/CSL inclusion complex was better than that of cisplatin (positive control). Meanwhile, the toxicity of CSL was slightly reduced after the formation of the inclusion complex with H1. Therefore, the complexes of CSL with H1-2 favor their use in anticancer drug formulations, broadening the field of application in clinic. [ABSTRACT FROM AUTHOR]

Inclusion complexes of three different lengths of polyamine modified β-cyclodextrins (β-CDs) (hosts 1-3) with baicalein (BC) were prepared by a solution stirring method, and characterized by UV-Vis spectroscopy, proton nuclear magnetic resonance, scanning electron microscopy, thermogravimetric analysis, and X-ray diffractometry. The results demonstrated that 1:1 inclusion complexes of hosts 1-3 with BC are present. The binding ability of hosts 1-3 towards BC increased according to the sequence H1 > H2 > H3, which was in good agreement with the decreasing chain lengths of these hosts. When compared to BC, the inclusion complexes produced 508-, 451- and 323-fold enhancement in water solubility, respectively. At low concentrations, inclusion complexes 1/BC and 3/BC were observed with a better capacity of scavenging when compared to that of free BC. These findings reflected that the complexation strengthened the antioxidant activity of BC. Moreover, the solubility in water and resistance to oxidation of hosts 1-3/BC were satisfactory, making it possible candidates for application in herbal medicine and as healthcare products. [ABSTRACT FROM AUTHOR]

Paclitaxel (PTX) is used to treat various cancers, but it also causes serious side effects and resistance. To better design similar compounds with less toxicity and more activity against drug-resistant tumors, it is important to clearly understand the PTX-binding pocket formed by the key residues of active sites on β-tubulin. Using a docking method, molecular dynamics (MD) simulation and density functional theory (DFT), we identified some residues (such as Arg278, Asp26, Asp226, Glu22, Glu27, His229, Arg369, Lys218, Ser277 and Thr276) on β-tubulin that are the active sites responsible for interaction with PTX. Another two residues, Leu371 and Gly279, also likely serve as active sites. Most of these sites contact with the 'southern hemisphere' of PTX; only one key residue interacts with the 'northern hemisphere' of PTX. These key residues can be divided into four groups, which serve as active compositions in the formation of an active pocket for PTX binding to β-tubulin. This active binding pocket enables a very strong interaction (the strength is predicted to be in the range of −327.8 to −365.7 kJ mol) between β-tubulin and PTX, with various orientated conformations. This strong interaction means that PTX possesses a high level of activity against cancer cells, a result that is in good agreement with the clinical mechanism of PTX. The described PTX pocket and key active residues will be applied to probe the mechanism of tumor cells resistant to PTX, and to design novel analogs with superior properties. [ABSTRACT FROM AUTHOR]