Molecular Aspects of -glycosides: Interactive Analysis of C-linked Compounds With the SGLT2 Molecular Model.

Background/aim: Interaction analysis between modeled human sodium/glucose cotransporter 2 (hSGLT2) and antidiabetic C-glycoside drugs, such as canagliflozin, dapagliflozin, ipragliflozin, empagliflozin, tofogliflozin, and luseogliflozin was performed.

Materials And Methods: The hSGLT2 was modeled using the X-ray data of Vibrio parahaemolyticus SGLT2 (protein data bank ID=2XQ2) as a template. Conformational analyses of C-glycosides were performed using CAChe-Conflex. Interactive analyses between hSGLT2 and C-glycosides were performed using Molegro Virtual Docker.

Results: Canagliflozin interacted with hSGLT2 via Asn, Ser, Lys and Gln Dapagliflozin interacted with six amino acids (Arg, Arg, Ile, Ser, Met and Ser). Ipragliflozin (Ala, Met and Gln), empagliflozin (Ser, Gly, Lys, Asp and Ser), tofogliflozin (Arg, Met, Ala, Ser and Ser), and luseogliflozin (Arg, Ser, Ser, Gly, His, Lys, Asp and Ser) interacted with hSGLT2 via the amino acids described in the parentheses.

Conclusion: The binding mode of each C-glycoside drug to hSGLT2 was different, and structural features of each compound were revealed. The reactive base points of C-glycosides were the sugar moiety, with the sugar structure being important for hSGLT2 inhibitory action.