1. Synthesis, molecular docking, and biological activities of new cyanopyridine derivatives containing phenylurea.
- Author
-
Gezegen H, Gürdere MB, Dinçer A, Özbek O, Koçyiğit ÜM, Taslimi P, Tüzün B, Budak Y, and Ceylan M
- Subjects
- Acetylcholinesterase metabolism, Butyrylcholinesterase metabolism, Cholinesterase Inhibitors chemical synthesis, Cholinesterase Inhibitors chemistry, Dose-Response Relationship, Drug, Glycoside Hydrolase Inhibitors chemical synthesis, Glycoside Hydrolase Inhibitors chemistry, Glycoside Hydrolases antagonists & inhibitors, Humans, Molecular Structure, Phenylurea Compounds chemistry, Pyridines chemical synthesis, Pyridines chemistry, Structure-Activity Relationship, Cholinesterase Inhibitors pharmacology, Glycoside Hydrolase Inhibitors pharmacology, Molecular Docking Simulation, Phenylurea Compounds pharmacology, Pyridines pharmacology
- Abstract
A new class of cyanopyridine derivatives (10a-e and 11a-e) containing the phenylurea unit was synthesized and tested against some metabolic enzymes including acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and α-glycosidase (α-Gly). The new cyanopyridine derivatives showed K
i values in the range of 40.73 ± 6.54 to 87.05 ± 16.98 µM against AChE, 29.17 ± 4.88 to 124.03 ± 22.43 µM against BChE, and 3.66 ± 0.93 to 26.33 ± 5.05 µM against α-Gly. These inhibition effects were compared with standard enzyme inhibitors like tacrine (for AChE and BChE) and acarbose (for α-Gly). Also, these cyanopyridine derivatives with the best inhibition score were docked into the active site of the indicated metabolic enzymes. Finally, molecular docking calculations were made to compare the biological activities of the compounds against AChE (-8.81 kcal/mol for molecule 11d), BChE (-3.52 kcal/mol for molecule 11d), and α-Gly (-2.98 kcal/mol for molecule 11a). After molecular docking calculations, the ADME/T analysis was performed to examine the future drug use properties of the new cyanopyridine derivatives containing phenylurea., (© 2020 Deutsche Pharmazeutische Gesellschaft.)- Published
- 2021
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