A dataset of 67 berberine derivatives for the inhibition of butyrylcholinesterase (BuChE) was studied based on the combination of quantitative structure–activity relationships models, molecular docking, and molecular dynamics methods. First, a series of berberine derivatives were reported, and their inhibitory activities toward butyrylcholinesterase (BuChE) were evaluated. By 2D- quantitative structure–activity relationships studies, the best model built by partial least-square had a conventional correlation coefficient of the training set (R²) of 0.883, a cross-validation correlation coefficient () of 0.777, and a conventional correlation coefficient of the test set () of 0.775. The model was also confirmed by Y-randomization examination. In addition, the molecular docking and molecular dynamics simulation were performed to better elucidate the inhibitory mechanism of three typical berberine derivatives (berberine, C2, and C55) toward BuChE. The predicted binding free energy results were consistent with the experimental data and showed that the van der Waals energy term (ΔE_vdw) difference played the most important role in differentiating the activity among the three inhibitors (berberine, C2, and C55). The developed quantitative structure–activity relationships models provide details on the fine relationship linking structure and activity and offer clues for structural modifications, and the molecular simulation helps to understand the inhibitory mechanism of the three typical inhibitors. In conclusion, the results of this study provide useful clues for new drug design and discovery of BuChE inhibitors from berberine derivatives.

The anti-influenza virus activities of 50 resveratrol (RV: 3, 5, 4′-trihydroxy-trans-stilbene) derivatives were evaluated using a neuraminidase (NA) activity assay. The results showed that 35 compounds exerted an inhibitory effect on the NA activity of the influenza virus strain A/PR/8/34 (H1N1) with 50% inhibitory concentration (IC₅₀) values ranging from 3.56 to 186.1 μm. Next, the 35 RV derivatives were used to develop 3D quantitative structure–activity relationship (3D QSAR) models for understanding the chemical–biological interactions governing their activities against NA. The comparative molecular field analysis (CoMFA r² = 0.973, q² = 0.620, q_test² = 0.661) and the comparative molecular similarity indices analysis (CoMSIA r² = 0.956, q² = 0.610, q_test² = 0.531) were applied. Afterward, molecular docking was performed to study the molecular interactions between the RV derivatives and NA. Finally, a cytopathic effect (CPE) reduction assay was used to evaluate the antiviral effects of the RV derivatives in vitro. Time-of-addition studies demonstrated that the RV derivatives might have a direct effect on viral particle infectivity. Our results indicate that the RV derivatives are potentially useful antiviral compounds for new drug design and development for influenza treatment.

Cabazitaxel is an anticancer drug and its marketed product (form A) is acetone solvate (1:1) (Didier E, Perrin MA. 2005. Patent WO2005/028462 A1). This work describes three crystal structures of cabazitaxel 1:1 solvates with isopropyl alcohol (B), 2-butanol (C), and dioxane (D). These solvates are isostructural with cabazitaxel forming a host framework through hydrogen bonds and the guest solvent molecules located in channels from which they can escape. The host is hydrogen bonded to each other through hydroxyl O₁ and sec-amide N₃′, whereas the hydroxyl O₂′ plays an important role in connecting the host to the guest. Moreover, because of the existence of channels in the crystal structure, the solvent-replacement method was established to prepare four new solvates of cabazitaxel with dimethyl formamide (E), cyclohexane (F), n-hexane (G), and ethyl ether (H). All the seven solvates involved in this work were proven to be isostructural by methods of X-ray crystallography and contain the same amount of solvents by thermogravimetric analysis. The single-crystal structures of solvate C–E and the solvates prepared by solvent-replacement method have been reported for the first time. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:1256–1262, 2015

Five solvates of betulinic acid with dimethyl sulfoxide (I), methanol (II), ethanol (III), isopropyl alcohol (IV), and 2-butanol (V) have been described in this work. Methods of X-ray crystallography, thermal analysis, and Fourier transform infrared spectroscopy were introduced for solvatomorphic identifications and characterizations. The orientation of isopropenyl and carboxylic groups might differ because of single-bonding rotations. The incorporation of solvents resulted in changes of the crystal symmetry, intermolecular arrangements, stoichiometry, hydrogen bonding interactions, and so on. Adducted solvents contributed most to the stability of crystal lattices and led to the formation of crystalline forms. Solvates II–V with their single-crystal structures determined have been reported for the first time. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:2696–2703, 2014

The flavonoid baicalein has been proven effective in animal models of parkinson's disease; however, the potential biological targets and molecular mechanisms underlying the antiparkinsonian action of baicalein have not been fully clarified. In the present study, the potential targets of baicalein were predicted by in silico target fishing approaches including database mining, molecular docking, structure-based pharmacophore searching, and chemical similarity searching. A consensus scoring formula has been developed and validated to objectively rank the targets. The top two ranked targets catechol-O-methyltransferase (COMT) and monoamine oxidase B (MAO-B) have been proposed as targets of baicalein by literatures. The third-ranked one (N-methyl-d-aspartic acid receptor, NMDAR) with relatively low consensus score was further experimentally tested. Although our results suggested that baicalein significantly attenuated NMDA-induced neurotoxicity including cell death, intracellular nitric oxide (NO) and reactive oxygen species (ROS) generation, extracellular NO reduction in human SH-SY5Y neuroblastoma cells, baicalein exhibited no inhibitory effect on [³H]MK-801 binding study, indicating that NMDAR might not be the target of baicalein. In conclusion, the results indicate that in silico target fishing is an effective method for drug target discovery, and the protective role of baicalein against NMDA-induced neurotoxicity supports our previous research that baicalein possesses antiparkinsonian activity.