Abstract
Type 2 diabetes mellitus (T2DM) is associated with pancreatic β-cell dysfunction and insulin resistance. Islet amyloid polypeptide (IAPP) aggregation is found to induce islet β-cell death in T2DM patients. Recently, we demonstrated that yakuchinone B derivative1exhibited inhibitory activity against IAPP aggregation. Thus, in this study, a series of synthesized yakuchinone B-inspired compounds were tested for their anti-IAPP aggregation activity. Four of these compounds,4e-h, showed greater activity than the lead compound1, in the sub-μM range (IC50= 0.7-0.8 μM). The molecular docking analysis revealed crucial hydrogen bonds between the compounds and residues S19 and N22 and important hydrophobic interactions with residue I26. Notably, compounds4gand4hsignificantly protected β-cells against IAPP-induced toxicity with EC50values of 0.1 and 0.2 μM, respectively. In contrast, the protective activities of compounds4eand4fwere weak. Overall, these results suggest that the compounds exhibiting IAPP aggregation-inhibiting activity have the potential to treat T2DM.
Original language | English |
---|---|
Pages (from-to) | 1096-1103 |
Number of pages | 8 |
Journal | Journal of Natural Products |
Volume | 84 |
Issue number | 4 |
DOIs | |
Publication status | Published - Apr 23 2021 |
ASJC Scopus subject areas
- Analytical Chemistry
- Molecular Medicine
- Pharmacology
- Pharmaceutical Science
- Drug Discovery
- Complementary and alternative medicine
- Organic Chemistry