Synthesis, density functional theory and kinetic studies of aminopyridine based α-glucosidase inhibitors.
Fazila RizviRaheel AhmedMuhammad Arslan BashirSaeed UllahHumaira ZafarAtia-Tul- WahabHina SiddiquiMouhamat Iqbal ChoudharyPublished in: Future medicinal chemistry (2023)
Aims: The current study aimed to develop new thiourea derivatives as potential α-glucosidase inhibitors for the management of hyperglycemia in patients of Type 2 diabetes, with a focus on identifying safer and more effective antidiabetic agents. Materials & methods: New thiourea derivatives ( 1-16 ) were synthesized through single-step chemical transformation and evaluated for in vitro α-glucosidase inhibition. Kinetic studies identified the mode of inhibition, free energy and type of interactions were analyzed through density functional theory and molecular docking. Results & conclusion: Compound 5 was identified as the most potent, noncompetitive and noncytotoxic inhibitor of α-glucosidase enzyme with half-maximal inhibitory concentration of 24.62 ± 0.94 μM. Computational studies reinforce experimental results, demonstrating significant enzyme interactions via hydrophobic and π-π stacking forces.
Keyphrases
- molecular docking
- density functional theory
- molecular dynamics
- molecular dynamics simulations
- case control
- end stage renal disease
- chronic kidney disease
- ejection fraction
- newly diagnosed
- heart rate
- blood pressure
- risk assessment
- ionic liquid
- resistance training
- oxidative stress
- climate change
- high intensity
- patient reported