Anti-α-Glucosidase, SAR Analysis, and Mechanism Investigation of Indolo[1,2-b]isoquinoline Derivatives

Abstract

To find potential α-glucosidase inhibitors, indolo[1,2-b]isoquinoline derivatives (1–20) were screened for their α-glucosidase inhibitory effects. All derivatives presented potential α-glucosidase inhibitory effects with IC50 values of 3.44 ± 0.36~41.24 ± 0.26 μM compared to the positive control acarbose (IC50 value: 640.57 ± 5.13 μM). In particular, compound 11 displayed the strongest anti-α-glucosidase activity, being ~186 times stronger than acarbose. Kinetic studies found that compounds 9, 11, 13, 18, and 19 were all reversible mix-type inhibitors. The 3D fluorescence spectra and CD spectra results revealed that the interaction between compounds 9, 11, 13, 18, and 19 and α-glucosidase changed the conformational changes of α-glucosidase. Molecular docking and molecular dynamics simulation results indicated the interaction between compounds and α-glucosidase. In addition, cell cytotoxicity and drug-like properties of compound 11 were also investigated.

Synthesis, Anti-Tyrosinase Activity, and Spectroscopic Inhibition Mechanism of Cinnamic Acid–Eugenol Esters

“…Figure 3 B shows the Lineweaver–Burk plots of substrate concentration and residual enzyme activity under compound c27 (0~4 μM). It could be observed that all lines with different slopes intersected in the second quadrant, suggesting compound c27 is a mixed-type inhibitor [ 51 , 52 ].…”

Synthesis of the chromone‐thiosemicarbazone scaffold as promising α‐glucosidase inhibitors: An in vitro and in silico approach toward antidiabetic drug design

“…Diabetes mellitus, represented as DM, is a chronic endocrine disease characterized by high blood glucose levels (hyperglycemia) and is a significant global health burden. [1,2] The major types of diabetes include type 1 diabetes (T1DM), developed as a result of the destruction of insulin-producing pancreatic β-cells, whereas type 2 diabetes (T2DM), the most prevalent form is characterized by insulin resistance and chronic hyperglycemia. Additionally, there is another type, gestational diabetes, occurring during pregnancy and posing risks to both mother and baby.…”