Synthesis, in vitro and in silico screening of 2-amino-4-aryl-6-(phenylthio) pyridine-3,5-dicarbonitriles as novel ? -glucosidase inhibitors
Author
Ali, M; Khan, KM; Mahdavi, M; Jabbar, A; Shamim, S; Salar, U; Taha, M; Perveen, S; Larijani, B; Faramarzi, MADate
2020-07-01Source Title
Bioorganic ChemistryPublisher
ACADEMIC PRESS INC ELSEVIER SCIENCEUniversity of Melbourne Author/s
Jabbar, AbdulAffiliation
Veterinary BiosciencesMetadata
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Journal ArticleCitations
Ali, M., Khan, K. M., Mahdavi, M., Jabbar, A., Shamim, S., Salar, U., Taha, M., Perveen, S., Larijani, B. & Faramarzi, M. A. (2020). Synthesis, in vitro and in silico screening of 2-amino-4-aryl-6-(phenylthio) pyridine-3,5-dicarbonitriles as novel ? -glucosidase inhibitors. BIOORGANIC CHEMISTRY, 100, https://doi.org/10.1016/j.bioorg.2020.103879.Access Status
This item is currently not available from this repositoryAbstract
Inhibition of α-glucosidase enzyme is of prime importance for the treatment of diabetes mellitus (DM). Apart of many organic scaffolds, pyridine based compounds have previously been reported for wide range of bioactivities. The current study reports a series of pyridine based synthetic analogues for their α-glucosidase inhibitory potential assessed by in vitro, kinetics and in silico studies. For this purpose, 2-amino-4-aryl-6-(phenylthio)pyridine-3,5-dicarbonitriles 1-28 were synthesized and subjected to in vitro screening. Several analogs, including 1-3, 7, 9, 11-14, and 16 showed many folds increased inhibitory potential in comparison to the standard acarbose (IC50 = 750 ± 10 µM). Interestingly, compound 7 (IC50 = 55.6 ± 0.3 µM) exhibited thirteen-folds greater inhibition strength than the standard acarbose. Kinetic studies on most potent molecule 7 revealed a competitive type inhibitory mechanism. In silico studies have been performed to examine the binding mode of ligand (compound 7) with the active site residues of α-glucosidase enzyme.
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