Paper Report for: Zhou_2020_Eur.J.Med.Chem_200_112415
Reference
Title: Simple analogues of natural product chelerythrine: Discovery of a novel anticholinesterase 2-phenylisoquinolin-2-ium scaffold with excellent potency against acetylcholinesterase Zhou B, Li H, Cui Z, Li D, Geng H, Gao J, Zhou L Ref: Eur Journal of Medicinal Chemistry, 200:112415, 2020 : PubMed
As simple analogues of the natural compound chelerythrine, a novel anti-cholinesterase 2-phenylisoquinolin-2-ium scaffold was designed by structure imitation. The activity evaluation led to the discovery of seven compounds with potent anti-acetylcholinesterase activity with IC50 values of =0.72 muM, superior to chelerythrine and standard drugs galantamine. Particularly, compound 8y showed the excellent dual acetylcholinesterase-butyrylcholinesterase inhibition activity, superior to rivastigmine, a dual cholinesterase inhibitor drug. Furthermore, the compounds displayed a competitive anti-acetylcholinesterase mechanism with the substrate and low cytotoxicity. Molecular docking showed that the isoquinoline moiety is embedded in a cavity surrounded by four aromatic residues of acetylcholinesterase by the pi-pi action. Structure-activity relationship showed that the p-substituents on the C-ring can dramatically improve the anti-acetylcholinesterase activity, while 8-OMe can increase the activity against the two cholinesterases simultaneously. Thus, the title compounds emerged as promising lead compounds for the development of novel cholinesterase inhibitor agents.
Zhou B, Li H, Cui Z, Li D, Geng H, Gao J, Zhou L (2020) Simple analogues of natural product chelerythrine: Discovery of a novel anticholinesterase 2-phenylisoquinolin-2-ium scaffold with excellent potency against acetylcholinesterase Eur Journal of Medicinal Chemistry200: 112415
Zhou B, Li H, Cui Z, Li D, Geng H, Gao J, Zhou L (2020) Eur Journal of Medicinal Chemistry200: 112415