Discovery of Novel Tryptanthrin Derivatives with Benzenesulfonamide Substituents as Multi-Target-Directed Ligands for the Treatment of Alzheimer's Disease.

ABSTRACT: Based on the multi-target-directed ligands (MTDLs) approach, two series of tryptanthrin derivatives with benzenesulfonamide substituents were evaluated as multifunctional agents for the treatment of Alzheimer's disease (AD). In vitro biological assays indicated most of the derivatives had good cholinesterase inhibitory activity and neuroprotective properties. Among them, the target compound 4h was considered as a mixed reversible dual inhibitor of acetylcholinesterase (AChE, IC₅₀ = 0.13 ± 0.04 μM) and butyrylcholinesterase (BuChE, IC₅₀ = 6.11 ± 0.15 μM). And it could also potentially prevent the generation of amyloid plaques by inhibiting self-induced Aβ aggregation (63.16 ± 2.33%). Molecular docking studies were used to explore the interactions of AChE, BuChE,

SUBMITTER: Wang G 

PROVIDER: S-EPMC10610214 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature