摘要：A series of A-B type sterically regular bicyclio[3.3.0] diene-based polymers were designed and synthesized as immobilized chiral diene ligands for asymmetric catalysis. With polymeric diene 6b, good to excellent enantiose- lectivities can be achieved in Rh-catalyzed asymmetric 1,4-addition of arylboronic acids to a,β-unsaturated ketones.

摘要：Beta-ketoacyl-acyl-carrier-protein synthase Ⅱ,an important enzyme in biosynthesis of bacterial fatty acid,is an attractive target in antibacterial drug design. Platensimycin(PTM), produced by Streptomyces platensis, has a strong, broad-spectrum Gram-positive antibacterial activity by selectively targeting to Fab F but exhibits no inhibition to the Fab F from Streptomyces platensis(spFabF). To study the self-resistance mechanism within the PTM-producing strain and provide hint for development of novel antibiotics, it is imperative to solve the structure of spFabF and elucidate the difference between spFabF and other Fab Fs which are not resistant to PTM. To this end, we constructed four chimeric Fab Fs based on the sequence of spFabF and its homologous protein after the expression of wide-type spFabF was failed. The crystal structure of one chimera, js_(200)FabF, of 91.2% sequence identity to spFabF,was solved. A structure comparison of js_(200)FabF with a PTM-bound Fab F suggested that three loops nearby the catalytic site might play key roles in preventing the binding of PTM to spFabF. The results provide an encouraging basis for further studies on the self-resistance mechanismand structure-based design of novel antibiotics targeting FabFs.

摘要：Since the PI3K signaling pathway is the most commonly activated in human cancers,inhibition of PI3K is a promising approach to cancer *** this study,a series of 2-methyl-5-nitrobenzeneacylhydrazones were designed and *** the new derivatives were tested by p110α enzymatic and Rh30 cellular *** enzyme selectivity profiling proved that 6e and 7 were potential selective PI3K inhibitors.

摘要：Acidic oligosaccharide sugar chain （AOSC）, a D-mannuronic acid oligosaccharide, derived from brownalgaepolysaccharide, has been completed Phase I clinical trial in China as an anti-Alzheimer＇s Disease （AD） drug candidate. The identification of AOSC-binding protein（s） in neurons is very important for understanding its action mechanism. To determine the binding protein（s） of AOSC in neurons mediating its anti-AD activities, confocal microscopy, affinity chromatography, and liquid chromatography-tandem mass spectrometry （LC-MS/MS） analysis were used. Confocal microscopy analysis shows that AOSC binds to SH-SY5Y cells in concentration-, time-, and temperature-dependent fashions. The AOSC binding proteins were purified by affinity chromatography and identified by LC-MS/MS analysis. The results showed that there are 349 proteins binding AOSC, including clathrin, adaptor protein-2 （AP-2） and amyloid precursor protein （APP）. These results suggest that the binding/entrance of AOSC to neurons is probably responsible for anti-AD activities.

摘要：A series of novel bis（trifluoroethyl）phosphonomethyl ether derivatives of acyclovir was synthesized and their in vitro anti-HBV activity was evaluated in HepG2 2.2.15 cells. In contrast to acyclovir, most of the described phosphonates emerged as potent inhibitors of HBV replication. Especially, the most active compound 11 with IC50 value of 2.92 μmol/L was 33 times more potent than acyclovir with ICso value of 100 μmol/L.

摘要：Objective：Although chondroprotective activities have been documented for polysaccharides,the potential target of different polysaccharide may *** study was aimed to explore the effect of glucan HBP-A in chondrocyte monolayer culture and chondrocytes-alginate hydrogel constructs in vivo,especially on the expression of type Ⅱ ***：Chondrocytes isolated from rabbit articular cartilage were cultured and verified by immunocytochemical staining of type Ⅱ *** viability was assessed after being treated with HBP-A in different *** status of chondrocytes-alginate hydrogel constructs in vitro was observed by scanning electron microscope（SEM）.The constructs were treated with HBP-A and then injected to nude mice *** weeks after transplantation,the specimens were observed through transmission electron microscopy（TEM）.The mRNA expressions of disintegrin and metalloproteinase with thrombospondin motifs 5（ADAMTs-5）,aggrecan and type Ⅱ collagen in both monolayer culture and constructs were determined by real time polymerase chain reaction（PCR）.The expression of typeⅡ collagen and matrix metalloproteinases-3（MMP-3） in chondrocyte monolayer culture was also tested through Western blot and enzyme linked immunosorbent assay（ELISA）,***：MMP-3 secretion and ADAMTs-5 mRNA expression in vitro were inhibited by HBP-A at 0.3 mg/mL *** morphological study,there were significant appearance of collagen in those constructs treated by ***,in both chondrocyte monolayer culture and chondrocytes-alginate hydrogel constructs,the expression of type Ⅱcollagen was increased significantly in HBP-A group when compared with control group（P〈0.001）.Conclusions：The study documented that the potential pharmacological target of glucan HBP-A in chondrocytes monolayer culture and tissue engineered cartilage in vivo may be concerned with the inhibition of catabolic enzymes MMP-3,ADAMTs-5,and increas

摘要：A series of novel triazole derivatives containing y-lactam were designed and synthesized, and their structures were confirmed by IH NMR, 13C NMR and HRMS, The in vitro antifungal activities of the target compounds were evaluated, The results showed that all of the compounds exhibited stronger activity against the six clinically important fungi tested than fluconazole. 3D and 3E showed comparative activity against the fungi tested except for Candida glabrata and Aspergillus fumigatus as voriconazole. In addition, the docking model for 2A and CYP51 was investigated.

摘要：GPR40 has emerged as an attractive drug target for the treatment of type 2 diabetes due to its role in the enhancement of insulin secretion with glucose dependency. With the aim to improve the metabolic and safety profiles, a series of novel phenylpropionic acid derivatives were synthesized. Extensive structural optimization led to identification of compounds 22 g and 23 e as potent GPR40 agonists with moderate liver microsomal stability. All the discovery supported further exploration surrounding this scaffold.

摘要：A novel series of pyrido[ 1,2-e]purin-4（3H）-one derivatives containing polar substituents on 5＇-position were designed and prepared as potential PDE5 inhibitors. This paper reports the synthetic routes, 1H-NMR data, and the PDE5 inhibitory activities of the target compounds. The polar piperazinyl group contained （on 5＇-position） compound, 3B2, showed the highest activity among the tested derivatives but less potency than sildenafil 1.

摘要：In order to find novel antifungal agents with good activity and aqueous solubility, a series of SYN-2869 analogues containing a pyridine ring were synthesized and evaluated for their in vitro antifungal activity and water solubility. The results indicated that some compounds showed potent activity against six pathogenic fungi. In particular, the analogue 17a having an isobutyl substitution on the triazolone exhibited significant broad spectrum antifungal activity. In addition, the water solubility of compound l？a was sufficiently improved over SYN-2869.