Structure–activity relationship studies of 4-benzyl-1H-pyrazol-3-yl β-d-glucopyranoside derivatives as potent and selective sodium glucose co-transporter 1 (SGLT1) inhibitors with therapeutic activity on postprandial hyperglycemia

Sodium glucose co-transporter 1 (SGLT1) plays a dominant role in the absorption of glucose in the gut and is considered a promising target in the development of treatments for postprandial hyperglycemia. A series of 4-benzyl-1H-pyrazol-3-yl β-d-glucopyranoside derivatives have been synthesized, and its inhibitory activity toward SGLTs has been evaluated. By altering the substitution groups at the 5-position of the pyrazole ring, and every position of the phenyl ring, we studied the structure–activity relationship (SAR) profiles and identified a series of potent and selective SGLT1 inhibitors. Representative derivatives showed a dose-dependent suppressing effect on the escalation of blood glucose levels in oral mixed carbohydrate tolerance tests (OCTT) in streptozotocin–nicotinamide-induced diabetic rats (NA-STZ rats).     

Plasmid DNA-induced Transformability of Yeast Cells during Spheroplast Conversion

Changes in transformability, regenerability, cell fusibilityand endocytotic activity of Saccharomyces cerevisiae yeast duringspheroplast conversion were investigated using the cell walldigesting enzyme Zymolylase. The transformability with plasmidDNA, cell fusibility and endocytotic activity all reached maximumat the critical spheroplast conversion period when about halfof the cells had been converted into spheroplasts. Lysosomotropicdrugs, chloroquine and dansylcadaverine enhanced transformationand endocytosis two- to threefold. This study showed that aclose relationship exists among transformability, cell fusingactivity and endocytotic activity of spheroplasts. ¹ A preliminary report appeared in ref. Yoshida and Takagi (1981). (Received March 15, 1982; Accepted May 12, 1982)     

Unique mechanism of plant endocytic/vacuolar transport pathways

The post-Golgi traffic network in plant cells is highly complex, which is correlated with the large number of genes related to this function. RABs and SNAREs are key regulators of tethering and fusion of transport vesicles to target membranes, and the numbers of these regulators have also expanded in plant lineages. In addition to this increase in the net number of genes, plants also seem to have evolved new gene families tailored to fulfill plant-unique functions. In this article, we summarize recent progress in studies on plant-unique RABs and SNAREs functioning in post-Golgi trafficking, with a special focus on the endocytic pathway. Takashi Ueda is the recipient of the BSJ Award for Young Scientist, 2007.     

Selective Inhibition by Pantoyl Lactone and Butyl Alcohol of the Initiation of DNA Replication in E. coli

We studied action mechanisms of pantoyl lactone and butyl alcohol on the macromolecular synthesis of E. coli. Protein synthesis was not significantly suppressed by these agents. DNA synthesis was more remarkably affected than RNA synthesis by them. Synchronous cultures of E. coli were subsequently used to investigate the inhibition of DNA replication with these agents. It was consequently shown that these agents inhibit the initiation of a new cycle of DNA replication in this organism but permit the completion of DNA replication initiated before addition of these agents to the medium.     

The Effects of Cyanate in Urea Solutions on the Gel Electrophoresis of the Subunits of Soybean 11S Globulin

For the screening of potent proteases of plant origin, gelatinolytic activities were measured for various vegetables and fruits. Green asparagus, kiwi fruit and miut were found to possess high proteolytic activities. Optimum temperatures for the activities of green asparagus and miut were 40 to 45°C and that of kiwi fruit was 60°C. Optimum pHs for the three activities were in neutral or slightly alkaline regions. The proteolytic enzymes of kiwi fruit and miut were stimulated by cysteine and EDTA but that of green asparagus was unaffected by them.