Exploring the Neuroprotective Effects of Some New Quinoxalines: A Novel Approach to Alzheimer's Disease Management

Abstract

Alzheimer's disease (AD) is a disabling neurodegenerative disorder characterized by irreversible cognitive decline, extracellular deposition of β-amyloid plaques, hyperphosphorylation of tau protein, oxidative stress, and neuroinflammation. Symptoms are all that present-day drugs offer, and they are powerless against arresting the progress of the disease. Recent studies indicate that quinoxalines—nitrogen-heterocyclic compounds—display neuroprotective effects by acting on several pathogenic mechanisms of AD. In the current research, new quinoxaline derivatives were prepared and screened for their antioxidant activity, AChE inhibitory activity, and anti-inflammatory activity both in vitro (PC12 cell line) and in vivo (APP/PS1 transgenic mice model). Results show that some derivatives, most notably QX-4 and QX-6, substantially enhanced neuronal viability, blocked Aβ-induced toxicity, decreased intracellular reactive oxygen species (ROS), and downregulated inflammatory cytokines. These results substantiate the therapeutic potential of quinoxalines in redressing the course of Alzheimer's disease. The antioxidant, anti-inflammatory, and cholinesterase-inhibiting activities combined in quinoxalines, especially QX-4, make them prime candidates for disease-modifying therapy in Alzheimer's. Their compact size and synthetic tractability are particularly advantageous, as they allow further SAR optimization and structure-activity relationship studies, which are in progress in our laboratory.