In Vitro Multi-Target Enzyme Inhibitory Potential of a Novel Trisamine Derivative against Acetylcholinesterase, Butyrylcholinesterase, Monoamine Oxidase-B and β-Secretase-1

Abstract

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline and multiple pathological mechanisms involving cholinergic dysfunction, oxidative stress, abnormal monoamine metabolism and amyloid-β accumulation. The development of multi-target-directed ligands capable of simultaneously modulating several disease-associated enzymes represents an attractive strategy in contemporary neuropharmacological research. The present study investigated the hypothetical in-vitro multi-target enzyme inhibitory potential of a novel trisamine derivative, designated SA-1, against acetylcholinesterase (AChE), butyrylcholinesterase (BChE), monoamine oxidase-B (MAO-B), and β-secretase-1 (BACE-1). The compound SA-1, previously characterized as a nitrogen-rich trisamine derivative with molecular formula C₂₄H₄₅N₇S₆ and molecular mass 624.03, was considered for enzyme-inhibition evaluation. Enzyme inhibition was expressed as percentage inhibition and IC₅₀ values. For research-planning purposes, hypothetical results suggested concentration-dependent inhibition against all four targets. SA-1 showed a stronger predicted inhibitory response toward MAO-B and AChE than toward BChE and BACE-1. The hypothetical IC₅₀ values were 18.42 ± 0.86 µM for AChE, 27.65 ± 1.12 µM for BChE, 12.74 ± 0.61 µM for MAO-B and 21.38 ± 0.94 µM for BACE-1. These illustrative findings suggest that trisamine scaffolds may provide a useful starting point for the development of multi-target neuroprotective agents. However, the presented numerical values are simulated for research and manuscript-development purposes and require experimental validation.

Keywords: Trisamine derivative; SA-1; acetylcholinesterase; butyrylcholinesterase; MAO-B; BACE-1; Alzheimer’s disease; multi-target inhibitor.