Cyclic diarylheptanoids as Na+-glucose cotransporter (SGLT) inhibitors from Acer nikoense

Discovery of Non-Glycoside Sodium-Dependent Glucose Co-Transporter 2 (SGLT2) Inhibitors by Ligand-Based Virtual Screening

“…However, the inhibition of SGLT2 was recovered when the tert-butyl group was replaced with hydrophobic groups, such as thiophene, furan, or phenyl (17,18,20,21). Since the tert-butyl group is mapped into the HY feature in the pharmacophore model, this result further validates that the HY feature is essential for inhibition to SGLT2 and further emphasizes that the hydrophobic group in this area is crucial for the activity.…”

Chapter 3. SGLT2 Inhibitors in Development

“…Following a recent report regarding weak SGLT inhibitory activity of selected members of the acerogenin family of natural product macrocycles, 56 the Green Cross group incorporated the dapagliflozin structure into 13-15 member macrocycles that linked C4 and C49 of 16. 57 Progressively decreasing the macrocycle size from a 15-membered to a 13-membered ring (see 2-14 and 2-15) increased SGLT2 inhibitory activity y2-fold to 60 nM; Ref.…”

Alstiphyllanines E–H, picraline and ajmaline-type alkaloids from Alstonia macrophylla inhibiting sodium glucose cotransporter

“…7 Recently, several new indole alkaloids were isolated from extracts of Alstonia species collected in Indonesia and Malaysia. 8,9 With an aim to isolate additional alkaloids against SGLT inhibitory activity, purification of extracts of A. macrophylla Wall.ex G. Don (Apocynaceae) collected in Indonesia led to four new alkaloids alstiphyllanines E-H (1-4) together with 16 known alkaloids (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20). Herein we report the isolation and structure elucidation of four new indole alkaloids, alstiphyllanines E-H (1-4) from A. macrophylla as well as SGLT inhibitory activity and structure activity relationship (SAR) study of some picraline-type indole alkaloids.…”