Scientists discover two coumarin-based molecules that inhibit key enzymes linked to post-meal blood sugar rises, offering potential avenues for novel diabetes therapies.
Researchers reporting in Scientific Reports say they have identified two coumarin-based compounds that showed notable activity against enzymes linked to after-meal blood sugar spikes, a finding that could inform the search for new diabetes treatments. The study examined 14 synthesised molecules and focused on their ability to inhibit alpha-glucosidase and alpha-amylase, two enzymes that help break down carbohydrates and can drive postprandial hyperglycaemia.
The strongest results came from two carbohydrazide derivatives. Compound 5 showed the most potent effect against alpha-glucosidase, with an IC50 value of 2.22 micrograms per millilitre, while compound 6 was the better alpha-amylase inhibitor at 2.98 micrograms per millilitre. Both outperformed acarbose, a standard drug used as a reference in the experiments. Computer modelling backed up the lab findings, with docking studies suggesting favourable binding to the target enzymes and molecular dynamics simulations indicating that the compound 5-alpha-glucosidase complex remained stable over 100 nanoseconds.
The authors also reported favourable binding free energy for compound 5 in MM-PBSA analysis, a method used to estimate how strongly a molecule binds to its target. In oral glucose tolerance tests, both leading compounds showed signs of glucose-lowering potential. The researchers said the results point to the importance of changes at the C-3 position and further optimisation at the 6th position of the coumarin ring, which they believe could help guide the design of next-generation small molecules aimed at controlling post-meal blood sugar.
Disclaimer: This content is for informational purposes only and is not intended to be a substitute for professional medical judgment, advice, diagnosis, or treatment.
