Targeting Type
2 Diabetes with <i>C</i>‑Glucosyl
Dihydrochalcones as Selective Sodium Glucose Co-Transporter 2 (SGLT2)
Inhibitors: Synthesis and Biological Evaluation
Ana R. Jesus
Diogo Vila-Viçosa
Miguel Machuqueiro
Ana P. Marques
Timothy M. Dore
Amélia P. Rauter
10.1021/acs.jmedchem.6b01134.s002
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
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.
2016-11-28 00:00:00
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