Zhou, Bohang published the artcileSimple analogues of natural product chelerythrine: Discovery of a novel anticholinesterase 2-phenylisoquinolin-2-ium scaffold with excellent potency against acetylcholinesterase, Application In Synthesis of 1885-29-6, the main research area is cholinesterase inhibitor mol docking butyrylcholinesterase SAR isoquinoline; Acetylcholinesterase; Benzo[c]phenanthridine; Butyrylcholinesterase; Isoquinoline; Molecular docking; Structure-activity relationship.
As simple analogs 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 ≤0.72μM, superior to chelerythrine and standard drugs galantamine. Particularly, compound 8y(I) 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. Mol. docking showed that the isoquinoline moiety is embedded in a cavity surrounded by four aromatic residues of acetylcholinesterase by the π-π 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.
European Journal of Medicinal Chemistry published new progress about Cholinesterase inhibitors. 1885-29-6 belongs to class nitriles-buliding-blocks, name is 2-Aminobenzonitrile(Flakes or Chunks), and the molecular formula is C7H6N2, Application In Synthesis of 1885-29-6.
Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts