Indole-pyridine carbonitriles: multicomponent reaction synthesis and bio-evaluation as potential hits against diabetes mellitus.
Mehwish SolangiKhalid Mohammed KhandXingyue JiMusa ÖzilNimet BaltaşUzma SalarAlamgir KhanZaheer Ul HaqHerchand MeghwarMuhammad TahaPublished in: Future medicinal chemistry (2023)
Background: Diabetes mellitus is a significant health disorder; therefore, researchers should focus on discovering new drug candidates. Methods: A series of indole-pyridine carbonitrile derivatives, 1-34 , was synthesized through a one-pot multicomponent reaction and evaluated for antidiabetic and antioxidant potential. Results: In this library, 12 derivatives - 1 , 2 , 4 , 5 , 7 , 8 , 10-12 , 14 , 15 and 31 - exhibited potent inhibitory activities against α-glucosidase and α-amylase enzymes, in comparison to acarbose (IC 50 = 14.50 ± 0.11 μM). Furthermore, kinetics, absorption, distribution, metabolism, excretion and toxicity and molecular docking studies were used to interpret the type of inhibition, binding energies and interactions of ligands with target enzymes. Conclusion: These results indicate that the compounds may be promising hits for controlling diabetes mellitus and its related complications.
Keyphrases
- molecular docking
- molecular dynamics simulations
- glycemic control
- oxidative stress
- healthcare
- human health
- public health
- anti inflammatory
- mental health
- type diabetes
- health information
- dna binding
- metabolic syndrome
- emergency department
- transcription factor
- density functional theory
- climate change
- electron transfer
- molecular dynamics
- aqueous solution