Synthesis and Acetylcholinesterase Inhibitory Evaluation of Coumarin‐Linked Carbazole Derivatives

Abstract

AbstractThe cholinesterase inhibitory activity was examined of synthetic carbazole‐coumarin hybrids, with long chain hydrocarbons, triazole, or piperazine as linkers. The most effective acetylcholinesterase inhibitor was 7‐((12‐(9H‐carbazol‐9‐yl)dodecyl)oxy)‐2H‐chromen‐2‐one (3 l), with an IC50 value of 6.86 μM and a high selectivity over butyrylcholinesterase. Compound 3 l also exhibited mixed‐type AChE inhibition in a kinetic study, with a Ki value of 4.87 μM. In addition, molecular docking of compound 3 l toward AChE was done to elucidate the inhibition at both the peripheral anionic and catalytic active sites. Furthermore, the HepG2 and Vero cells were unaffected by toxicity from compound 3 l. Therefore, these findings could be exploited to create a number of carbazole‐coumarin hybrids for future potential treatments for Alzheimer's disease.