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

Rima D AlharthySana KhalidShamool FatimaSaeed UllahAjmal KhanSuraj Narayan MaliRahul D JawarkarSanjay S DhabardeHamdy KashtohParham TaslimiAhmed Al-HarrasiZahid ShafiqNader M Boshta
Published in: Archiv der Pharmazie (2024)
Diabetes is a serious metabolic disorder affecting individuals of all age groups and prevails globally due to the failure of previous treatments. This study aims to address the most prevalent form of type 2 diabetes mellitus (T2DM) by reporting on the design, synthesis, and in vitro as well as in silico evaluation of chromone-based thiosemicarbazones as potential α-glucosidase inhibitors. In vitro experiments showed that the tested compounds were significantly more potent than the standard acarbose, with the lead compound 3n exhibiting an IC 50 value of 0.40 ± 0.02 μM, ~2183-fold higher than acarbose having an IC 50 of 873.34 ± 1.67 μM. A kinetic mechanism analysis demonstrated that compound 3n exhibited reversible inhibition of α-glucosidase. To gain deeper insights, in silico molecular docking, pharmacokinetics, and molecular dynamics simulations were conducted for the investigation of the interactions, orientation, stability, and conformation of the synthesized compounds within the active pocket of α-glucosidase.
Keyphrases
  • molecular docking
  • molecular dynamics simulations
  • type diabetes
  • cardiovascular disease
  • glycemic control
  • adipose tissue
  • climate change
  • human health