| DOI: 10.29090/psa.2025.03.25.3874 | Pharm Sci Asia 2025; 52(3), 396-416 |
Exploration of potential natural dual inhibitors of SGLT1 and SGLT2 for the treatment of type 2 diabetesKhoi Anh Nguyen, Phuong Thuy Viet Nguyen*, Kiet Hoang Anh Nguyen
- Faculty of Pharmacy, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City 700000, Viet Nam
Dual inhibitors of both sodium-glucose cotransporters (SGLT1 and 2) is of great interest due to combination of blocking renal SGLT2 as well as intestinal SGLT1 leading to decreases of glucose absorption and HbA1C and also increase of GLP-1 and beneficial effect on cardiovascular system1. Thus, this study aimed to explore potential natural drugs targeting both SGLT1 and SGLT2 proteins for the treatment of type 2 diabetes. The screening process through combining pharmacophore models drived from molecular dynamics simulations (MDs) and molecular docking for both structures of SGLT1 (PDB: 7WMV) and SGLT2 (PDB: 7VSI) were successfully applied. Seven potential natural dual SGLT1 and SGLT2 inhibitors were obtained including neodiosmin, apigenin-7-O-neohesperidosid, neobudoffieid, pinoresinol diflucosid, hispidulin-7-O-rutinosid, apigenin-7-O-rutinosid, syringaresinol-4-O-β-D-glucopyranosid). They satisfied the five features of two pharmacophore models for SGLT1 and SGLT2 proteins for their inhibitory bioactivities. Docking results showed that they fitted well in the binding sites of both proteins by forming key interactions similar to a reference dual inhibitor, sotagliflozin with their binding affinities ranging from -10.07 to -13.67 kcal.mol-1 for SGLT1 and from -10.56 to -13.90 kcal.mol-1 for SGLT2. Further experimental assays are required for testing bioactivities of these seven compounds as dual SGLT1 and 2 inhibitors.
Keyword:
sodium-glucose cotransporter, dual SGLT1 and SGLT2 inhibitors, pharmacophore models, molecular dynamics simulation, molecular docking, virtual screening
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