Affiliation:
1. Department of Chemistry Faculty of Science Kasetsart University Bangkok 10900 Thailand
2. Center of Excellence for Innovation in Chemistry Special Research Unit for Advanced Magnetic Resonance Faculty of Science Kasetsart University Bangkok 10900 Thailand
3. Central Laboratory and Greenhouse Complex Research and Academic Service Center Faculty of Agriculture at Kamphaeng Saen Kasetsart University Kamphaeng Saen Campus Nakhon Pathom 73140 Thailand
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.
Funder
Center of Excellence for Innovation in Chemistry