Jesus, Ana R. Vila-Viçosa, Diogo Machuqueiro, Miguel Marques, Ana P. Dore, Timothy M. Rauter, Amélia P. Targeting Type 2 Diabetes with <i>C</i>‑Glucosyl Dihydrochalcones as Selective Sodium Glucose Co-Transporter 2 (SGLT2) Inhibitors: Synthesis and Biological Evaluation Inhibiting glucose reabsorption by sodium glucose co-transporter proteins (SGLTs) in the kidneys is a relatively new strategy for treating type 2 diabetes. Selective inhibition of SGLT2 over SGLT1 is critical for minimizing adverse side effects associated with SGLT1 inhibition. A library of <i>C</i>-glucosyl dihydrochalcones and their dihydrochalcone and chalcone precursors was synthesized and tested as SGLT1/SGLT2 inhibitors using a cell-based fluorescence assay of glucose uptake. The most potent inhibitors of SGLT2 (IC<sub>50</sub> = 9–23 nM) were considerably weaker inhibitors of SGLT1 (IC<sub>50</sub> = 10–19 μM). They showed no effect on the sodium independent GLUT family of glucose transporters, and the most potent ones were not acutely toxic to cultured cells. The interaction of a <i>C</i>-glucosyl dihydrochalcone with a POPC membrane was modeled computationally, providing evidence that it is not a pan-assay interference compound. These results point toward the discovery of structures that are potent and highly selective inhibitors of SGLT2. POPC;Selective Sodium Glucose Co-Transporter 2;GLUT;cell-based fluorescence assay;type 2 diabetes;sodium glucose co-transporter proteins;SGLT 1;SGLT 2;inhibitor;pan-assay interference compound;Targeting Type 2 Diabetes;IC 50;Biological Evaluation Inhibiting glucose reabsorption;SGLT 1 inhibition 2016-11-28
    https://acs.figshare.com/articles/dataset/Targeting_Type_2_Diabetes_with_i_C_i_Glucosyl_Dihydrochalcones_as_Selective_Sodium_Glucose_Co-Transporter_2_SGLT2_Inhibitors_Synthesis_and_Biological_Evaluation/4560634
10.1021/acs.jmedchem.6b01134.s002