Carltonine-derived compounds for targeted butyrylcholinesterase inhibition.

ABSTRACT: The investigation into human butyrylcholinesterase (hBChE) inhibitors as therapeutic agents for Alzheimer's disease (AD) holds significant promise, addressing both symptomatic relief and disease progression. In the pursuit of novel drug candidates with a selective BChE inhibition pattern, we focused on naturally occurring template structures, specifically Amaryllidaceae alkaloids of the carltonine-type. Herein, we explored a series of compounds implementing an innovative chemical scaffold built on the 3- and 4-benzyloxy-benzylamino chemotype. Notably, compounds 28 (hBChE IC₅₀ = 0.171 ± 0.063 μM) and 33 (hBChE IC₅₀ = 0.167 ± 0.018 μM) emerged as top-ranked hBChE inhibitors. In silico simulations elucidated the binding modes of these c

SUBMITTER: Pidany F 

PROVIDER: S-EPMC11110763 | biostudies-literature | 2024 May

REPOSITORIES: biostudies-literature