Multifunctional, Fluorene-Based Modulator of Cholinergic and GABAergic Neurotransmission as a Novel Drug Candidate for Palliative Treatment of Alzheimer's Disease.

ABSTRACT: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by memory loss and behavioral and psychological symptoms of dementia (BPSD). Given that cholinergic neurons are predominantly affected in AD, current treatments primarily aim to enhance cholinergic neurotransmission. However, imbalances in other neurotransmitters, such as γ-aminobutyric acid (GABA), also contribute to AD symptomatology. In the presented research, using a combination of crystallography and computational methods we developed compound 6 as a dual modulator of GABAergic and cholinergic neurotransmission systems. Compound 6 demonstrated inhibition of BuChE (IC₅₀=0.21 μM) and GABA transporter 1 (IC₅₀=10.96 μM) and 3 (IC₅₀=7.76 μM), along with a favorable drug-likeness profile.

SUBMITTER: Panek D 

PROVIDER: S-EPMC11796312 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature