Synthesis, molecular docking, and biological activities of new cyanopyridine derivatives containing phenylurea

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 alpha-glycosidase (alpha-Gly). The new cyanopyridine derivatives showed K-i values in the range of 40.73 +/- 6.54 to 87.05 +/- 16.98 mu M against AChE, 29.17 +/- 4.88 to 124.03 +/- 22.43 mu M against BChE, and 3.66 +/- 0.93 to 26.33 +/- 5.05 mu M against alpha-Gly. These inhibition effects were compared with standard enzyme inhibitors like tacrine (for AChE and BChE) and acarbose (for alpha-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 alpha-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.