Construction and Screening of Fractional Library of Salviae Miltiorrhizae Radix et Rhizoma for the Rapid Identification of Active Compounds against Prostate Cancer.

Efficient screening of anticancer agents is in urgent need to develop new drugs that combat malignant tumors and drug resistance. In this study, a combined strategy composed by solvent partition and HPLC fractionation was developed to generate an herbal fraction library of Salviae Miltiorrhizae Radix et Rhizoma to quickly and efficiently screen anticancer agents. All library entries are directed into 96 well plates which are well mapped with HPLC chromatograms. The cell proliferation assay revealed seven active subfractions. Then, the major active ten peaks in these subfractions were prepared and isolated by semipreparative HPLC, and their inhibitory activities against prostate cancer cells were then tested at the same concentration level, leading to the identification of several active compounds. In addition, the structures of compounds arucadiol (2), 15,16-dihydrotanshinone I (4), methyl tanshinonate (5), cryptanshinone (7), 1,2-dihydrotanshinquinone I (9), and tanshinone IIA (10) were characterized by mass spectrometry and X-ray crystallographic analysis, and they were confirmed to be active in suppressing prostate cancer cell proliferation at 7.5 or 15 µg/mL, among which, the minor compounds 2, 4, and 5 showed higher activities than 9 and 10. This study provided a rapid strategy of identifying new anticancer agents in Salviae Miltiorrhizae Radix et Rhizoma, which can be applied in other herbal medicines.

Probing the stereoselectivity of OleD-catalyzed glycosylation of cardiotonic steroids.

The glycosyltransferase OleD variant as a catalyst for the glycosylation of four pairs of epimers of cardiotonic steroids (CTS) are assessed. The results of this study demonstrated that the OleD-catalyze glycosylation of CTS is significantly influenced by the configuration at C-3 and the A/B fusion mode. 3ß-OH and A/B ring cis fusion are favoured by OleD (ASP). An epoxide ring at C-14 and C-15 further increases the bioconversion rate; while an acetyl group at C-16 and lactone ring type at C-17 did not influence the biotransformation. A high conversion rate corresponded to a low K m value. A molecular docking simulation showed that filling of hydrophobic pocket II and interaction with residue Tyr115 may play an important role in the glycosylation reactions catalyzed by OleD glycosyltransferases. Furthermore, the glycosylation products showed a stronger inhibitory activity for Na+, K+-ATPase than the corresponding aglycones. This study provides the first stereoselective properties for OleD (ASP) catalyzed glycosylation.

Isolation, chemotaxonomic significance and cytotoxic effects of quassinoids from Brucea javanica.

A new quassinoid, bruceene A (1) along with seventeen known quassinoids (2-18) was isolated from the fruits of Brucea javanica. The structure of 1 was elucidated by extensive spectroscopic methods, and was further confirmed by single-crystal X-ray diffraction analysis. Isolation of similar quassinoids 1-3 as those in genus Ailanthus from genus Brucea, indicated the close chemotaxonomic relationship between these two genera, which further supported the phylogenetic study by DNA analysis. Compounds 5, 7, 10 and 12 with a 3-hydroxy-3-en-2-one moiety showed potent inhibitory activities against the MCF-7 and MDA-MB-231 cells with IC50 values in the ranges 0.063-0.182 µM and 0.081-0.238 µM, respectively; while glycosidation at 3-OH significantly decreased the cytotoxicity. It was also found that the most potent compound 7 induced apoptosis in MCF-7 cells via the intrinsic mitochondrial apoptotic pathway.

Gallic acid pyridine monosolvate.

IN THE TITLE COMPOUND (SYSTENATIC NAME: 3,4,5-trihy-droxy-benzoic acid pyridine monosolvate), C(5)H(5)N·C(7)H(6)O(5), the gallic acid mol-ecule is essentially planar (r.m.s deviation = 0.0766 Šfor non-H atoms) and is linked to the pyridine mol-ecule by an O-H⋯N hydrogen bond. An intra-molecular O-H⋯O hydrogen bond occurs in the gallic acid mol-ecule. The gallic acid and pyridine mean planes make a dihedral angle 12.6 (3)°. Inter-molecular O-H⋯O and O-H⋯N hydrogen bonding involving the hy-droxy and carboxyl groups and the pyridine mol-ecule, and π-π inter-actions between inversion-related pyridines [centroid-centroid distance = 3.459 (6) Å] and between pyridine and benzene rings [centroid-centroid distance = 3.548 (6) Å], lead to a three-dimensional network in the crystal.