Synthesis, Biological Evaluation and Machine Learning Prediction Model for Fluorinated Cinchona Alkaloid-Based Derivatives as Cholinesterase Inhibitors.

ABSTRACT: A series of 46 Cinchona alkaloid derivatives that differ in positions of fluorine atom(s) in the molecule were synthesized and tested as human acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitors. All tested compounds reversibly inhibited AChE and BChE in the nanomolar to micromolar range; for AChE, the determined enzyme-inhibitor dissociation constants (K_i) ranged from 3.9-80 µM, and 0.075-19 µM for BChE. The most potent AChE inhibitor was N-(para-fluorobenzyl)cinchoninium bromide, while N-(meta-fluorobenzyl)cinchonidinium bromide was the most potent BChE inhibitor with K_i constant in the nanomolar range. Generally, compounds were non-selective or BChE selective cholinesterase inhibitors, where N<

SUBMITTER: Ramic A 

PROVIDER: S-EPMC9610298 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature