Synthesis, pharmacology and molecular docking on multifunctional tacrine-ferulic acid hybrids as cholinesterase inhibitors against Alzheimer's disease.

ABSTRACT: The cholinergic hypothesis has long been a "polar star" in drug discovery for Alzheimer's disease (AD), resulting in many small molecules and biological drug candidates. Most of the drugs marketed for AD are cholinergic. Herein, we report our efforts in the discovery of cholinesterases inhibitors (ChEIs) as multi-target-directed ligands. A series of tacrine-ferulic acid hybrids have been designed and synthesised. All these compounds showed potent acetyl-(AChE) and butyryl cholinesterase(BuChE) inhibition. Among them, the optimal compound 10g, was the most potent inhibitor against AChE (electrophorus electricus (eeAChE) half maximal inhibitory concentration (IC₅₀) = 37.02 nM), it was also a strong inhibitor against BuChE (equine serum (eqBuChE) IC₅₀ = 101.40 nM). Besid

SUBMITTER: Zhu J 

PROVIDER: S-EPMC6010002 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature