Indole-pyridine carbonitriles: multicomponent reaction synthesis and bio-evaluation as potential hits against diabetes mellitus
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2023Author
Solangi, MehwishKhan, Khalid Mohammed
Ji, Xingyue
Özil, Musa
Baltaş, Nimet
Salar, Uzma
Khan, Alamgir
Ul-Haq, Zaheer
Meghwar, Herchand
Taha, Muhammad
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Solangi, M., Khan, K. M., Ji, X., Özil, M., Baltaş, N., Salar, U., Khan, A., Haq, Z. U., Meghwar, H., & Taha, M. (2023). Indole-pyridine carbonitriles: multicomponent reaction synthesis and bio-evaluation as potential hits against diabetes mellitus. Future medicinal chemistry, 10.4155/fmc-2023-0087. Advance online publication. https://doi.org/10.4155/fmc-2023-0087Abstract
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 (IC50 = 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.