Synthesis, characterization, crystal structure and evaluation of four carbazole-coumarin hybrids as multifunctional agents for the treatment of Alzheimer's disease

Publication date: Available online 13 February 2020Source: Journal of Molecular StructureAuthor(s): Da-Hua Shi, Wei Min, Meng-qiu Song, Xin-Xin Si, Ming-Cheng Li, Zhao-yuan Zhang, Yu-Wei Liu, Wei-Wei LiuAbstractCoupling of two distinct pharmacophores, carbazole and coumarin, endowed with different biological properties, afforded four hybrid compounds. The structures of the carbazole-coumarin hybrids were characterized by FT-IR, NMR, HRMS and single-crystal X-ray diffraction studies. All of these compounds exhibited significant acetylcholinesterase inhibitory activities. Among them, compound 4-((5-(9H-carbazol-9-yl)pentyl)oxy)-2H-chromen-2-one (3d) exhibited the best inhibition activity with IC50 of 3.75 μM for acetylcholinesterase from electric eel and 70.51 μM for human recombinant acetylcholinesterase. Moreover, the compound 7-(3-(9H-carbazol-9-yl propoxy)-4-methyl-2H-chromen-2-one (3a) had the best antioxidant activity. The docking studies demonstrated that compound 3d could interact with both the catalytic active site and the peripheral anionic site of acetylcholinesterase. These attributes imply carbazole-coumarin hybrids as multifunctional agents for the Alzheimer's disease treatment.Graphical abstract
Source: Journal of Molecular Structure - Category: Molecular Biology Source Type: research