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

Coupling 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 IC 50 of 3.75  μ M for acetylcholinesterase from electric eel and 70.51  μ M 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.