Synthesis and antifungal activities of N-1,3,4-thiadiazol-2-yl-4-oxo-thiochroman-2-yl-formamide derivatives / 药学学报

Thiochromanones and 1,3,4-thiadazoles as heterocyclic compounds have broad biological activities. In order to find novel compounds with antifungal bioactivity, substituted thiophenol and maleic anhydride were used to synthesize the intermediate 4-oxothiochromane-2-carboxylic acid. It was reacted with 2-amino-1,3,4-thiadiazol to get fourteen target compounds containing 1,3,4-thiadazole moiety. The structures of the obtained compounds were confirmed by 1H NMR, 13C NMR and HR-MS. All compounds were investigated for antifungal activity via microdilution broth method. The results showed that the target compounds 3a and 3c to Epidermophyton floccosum and Mucor racemosus exhibited better antifungal activity than the positive control fluconazole, in which the minimum inhibition concentration can reach 8 μg·mL-1 and 16 μg·mL-1. Compound 3e showed significant inhibitory activity to Helminthosporium maydis, Sclerotinia sclerotiorum and Botrytis cinerea compared with that of the positive control carbendazim. Compound 3b exhibited inhibitory activity to Helminthosporium maydis better than the positive control carbendazim.

Synthesis, biological activity and molecular docking research of N-{(4-oxo-thiochroman-3-yl)phenyl-methyl}acetamide derivatives as α-glucosidase inhibitors / 药学学报

In order to develop potent antidiabetic agents that have inhibitory effect to a-glucosidase, twelve β-acetamido ketone derivatives such as N-{[(substituted-4-oxo-thiochroman-3-yl)phenyl]-methyl}acetamide are designed and synthesized through one-pot Dakin-West reaction. Their chemical structures are confirmed by 1H NMR, 13C NMR, IR and HR-MS. In vitro α-glucosidase inhibition assays of compounds 4a-41 were carried out using glucose oxidase method. The result indicated that most of them possess inhibitory activity in vitro. Compound 4k showed the most potent inhibitory activity with 87.3% inhibition of α-glucosidase at the concentration of 5.39 mmol x L(-1). The structure-activity relationship of these β-acetamido ketone derivatives was discussed preliminarily. Moreover, the molecular docking method was used to study the interaction mode of compound 4k and α-glucosidase. Our results will be helpful for designing of α-glucosidase inhibitors in the future.

Synthesis, biological activity and molecular docking research of N-{(4-oxo-thiochroman-3-yl)phenyl-methyl}acetamide derivatives as α-glucosidase inhibitors / 药学学报

In order to develop potent antidiabetic agents that have inhibitory effect to α-glucosidase, twelve β-acetamido ketone derivatives such as N-{[(substituted-4-oxo-thiochroman-3-yl)phenyl]-methyl}acetamide are designed and synthesized through one-pot Dakin-West reaction. Their chemical structures are confirmed by 1H NMR, 13C NMR, IR and HR-MS. In vitro α-glucosidase inhibition assays of compounds 4a-4l were carried out using glucose oxidase method. The result indicated that most of them possess inhibitory activity in vitro. Compound 4k showed the most potent inhibitory activity with 87.3% inhibition of α-glucosidase at the concentration of 5.39 mmol·L-1. The structure-activity relationship of these β-acetamido ketone derivatives was discussed preliminarily. Moreover, the molecular docking method was used to study the interaction mode of compound 4k and α-glucosidase. Our results will be helpful for designing of α-glucosidase inhibitors in the future.

Effect of cyclosporine A on the Pl - 3 k pathway in proliferation of rat lens epithelial cells / 国际眼科杂志(Guoji Yanke Zazhi)

AlM:To investigate the effect of cyclosporine A ( CsA) on the phosphatidylinositol-3 kinase ( Pl-3k ) pathway during procession of proliferation in epithelial cells of rabbit lens, and provide treatment strategies for after cataract on the basis of experiment. METHODS: Sixty eyes of 30 healthy white rabbits were operated by lens cortex removal in cataract surgery, and 30 right eyes were divided in treatment group and the other 30 eyes were divided in control group. From the first postoperative day, the control group eyes were dropped with normal saline 6 times each day, and the treatment group eyes were dropped with 1% CsA 6 times each day. Six rabbits were selected randomly and killed on the day before dropping and 1, 2wk, 1 and 2mo of postoperative day respectively. The lens of those killed rabbits were removed by surgery. The strategies of immunohistochemistry and mount in situ hybridization were used to detect the content of proliferating cell nuclear antigen ( PCNA) , gene of phosphate and tension homology deleted on chromsome ten ( PTEN) mRNA, Ser473-R, respectively. RESULTS:The expression of PCNA and Ser473-R were both down-regulate after operation in treatment group and control group, and the PCNA levels were significantly lower among treatment group than those in control group on 1wk (0.690±0.035 vs 0.785±0.015, t=6.099, P CONCLUSlON:1% CsA could inhibit the proliferation of epithelial cells in lens of rabbits with after cataract through preventing Pl-3k pathway.