TAG E

In this study, we have investigated the potential of two classes of thioglucoside analogs of gliflozins as antidiabetic drugs, one with substitutions of S-atoms in meta-positions (similar to C-glucoside SGLT2 inhibitors, TAGs A, B, and C) and the other with substitutions of S-atoms in ortho-positions (similar to O-glucoside SGLT2 inhibitors, TAGs D, E, F, and G).These TAGs were confirmed to show good stability against β-glucosidase and to have no acute toxicity to cultured cells.Most importantly, TAGs D, E, F, and G all showed high inhibitory activity against SGLT2 (IC₅₀: 2.0-5.9 nM) and thus have great potential to be developed as new gliflozin drugs.Compared with the synthesis of C-glucoside gliflozins, the synthesis of TAGs is simple, efficient, and associated with low costs, high yields, and very mild reaction conditions.