New carbazole-thiadiazole compounds as inhibitors of enzymes involved in sugar digestion: design, testing, and computer analysis

The compound 5l is identified as the most potent inhibitor of α-amylase with an IC value of 0.68 µM, significantly outperforming acarbose.

• 5r shows dual inhibitory activity against α-amylase and α-glucosidase with IC values of 1.63 µM and 0.14 µM, respectively.
• The synthesized compounds exhibit low cytotoxicity on hepatic stellate (LX-2) cells, suggesting safety for therapeutic use.
• Molecular docking studies indicate strong binding interactions through hydrogen bonding and hydrophobic interactions with active site residues.
• Density functional theory (DFT) and electrostatic potential (ESP) analyses provide insights into the electronic properties and structure-activity relationships.
• Pharmacokinetic profiling using the BOILED-Egg model suggests these derivatives have excellent oral bioavailability and drug-likeness.

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