Abstract
Acetylcholinesterase (AChE) and β-secretase (BACE-1) have become attractive therapeutic targets for Alzheimer’s disease (AD). Flavones are flavonoid derivatives with various bioactive effects, including AChE and BACE-1 inhibition. In the present work, a series of 14 flavone derivatives was synthesized in relatively high yields (35–85%). Six of the synthetic flavones (B4, B5, B6, B8, D6 and D7) had completely new structures. The AChE and BACE-1 inhibitory activities were tested, giving pIC50 3.47–4.59 (AChE) and 4.15–5.80 (BACE-1). Three compounds (B3, D5 and D6) exhibited the highest biological effects on both AChE and BACE-1. A molecular docking investigation was conducted to explain the experimental results. These molecules could be employed for further studies to discover new structures with dual action on both AChE and BACE-1 that could serve as novel therapies for AD.
Highlights
Alzheimer’s disease (AD) is an irreversible neurodegenerative disorder with the defects in nervous system and cognitive function [1]
The results indicated that all studied substances were successfully docked into the binding pockets of AChE and BACE-1 with the docking scores of (−10.36)–(−27.06)
The results indicated that all studied substances were successfully docked into the binding pockets of AChE and BACE-1 with the docking scores (A)
Summary
Alzheimer’s disease (AD) is an irreversible neurodegenerative disorder with the defects in nervous system and cognitive function [1]. In this ailment, there is an impairment of the cerebral cortex with complex processes; involving the production of senile plaques, neurofibrillary tangles, synapse loss and neuroinflammation; leading to the progressive cognitive decline and memory loss [2,3]. Discovery of novel drugs for AD is an urgent task. The exact pathogenesis of AD is currently not fully know and this disease might be referred to as a neurological disorder caused by multiple factors, such as: (i) low concentrations of acetylcholine (ACh) in synaptic clefts; (ii) the accumulation of intracellular neurofibrillary tangles with hyperphosphorylated. The multifactorial nature of AD has transformed the paradigm of AD drug
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