Synthetic Xanthone Derivatives as Multifunctional Therapeutics for Alzheimer’s Disease: Chemistry, Mechanisms and Future Perspectives

Abstract

Introduction: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline and memory loss, with limited effective therapeutic options available. Synthetic xanthone derivatives have recently garnered attention due to their diverse pharmacological properties and potential to target multiple AD pathological pathways. Methods: This review comprehensively analyzes recent advances in the synthesis, chemical modifications, and biological activities of synthetic xanthone derivatives relevant to AD. Literature from various databases was critically evaluated, focusing on structure activity relationships (SAR), mechanisms of action, pharmacokinetics, and drug delivery approaches. Emphasis was placed on multidisciplinary strategies integrating medicinal chemistry, pharmacology, and neuroscience to accelerate therapeutic development. Results: Synthetic xanthones demonstrate multiple bioactivities including antioxidant, anti-inflammatory, acetylcholinesterase inhibitory, and anti-amyloidogenic effects, contributing to their neuroprotective potential. SAR studies and computational modeling have identified key structural motifs that enhance potency and selectivity for AD targets. However, challenges such as limited blood–brain barrier permeability and In vivo efficacy require innovative drug delivery systems, including nanocarriers and prodrug strategies. The review highlights successful preclinical studies showcasing cognitive improvements and neuropathological mitigation in AD models. Conclusion: Synthetic xanthone derivatives represent a promising scaffold for multi-targeted AD therapy. Future research should focus on optimizing pharmacokinetic properties, expanding In vivo validation, and clinical translation through a collaborative multidisciplinary approach. Harnessing advances in chemistry, biology, and drug delivery will be critical to realize the therapeutic potential of xanthone-based compounds and address the unmet needs in Alzheimer’s disease treatment.