Recent advances in Xanthone-based molecular hybrids: emerging therapeutic strategies for multifactorial diseases

Multifactorial diseases such as cancer, diabetes, neurodegenerative and inflammatory disorders remain major global health challenges due to their complex pathophysiology and limited therapeutic options. Xanthones (9 H-xanthen-9-ones), a class of oxygenated heterocycles with a dibenzo-γ-pyrone scaffold, have emerged as privileged structures in drug discovery owing to their exceptional structural diversity and broad spectrum of biological activities. This review highlights recent advances in the design and development of xanthone-based molecular hybrids, which integrate multiple bioactive pharmacophores to achieve multitarget or synergistic therapeutic effects. Structure-activity relationship (SAR) and quantitative structure-activity relationship (QSAR) studies have elucidated key functional modifications such as hydroxylation, prenylation, and hybridization with heterocyclic or amino alkyl groups-that significantly enhance potency, selectivity, and safety. Natural and synthetic xanthone derivatives have demonstrated promising antibacterial, anticancer, anti-inflammatory, antioxidant, antidiabetic, and neuroprotective properties, with molecular targets ranging from COX-2 and α-glucosidase to topoisomerase II and cholinesterase. Triazole-, thiazole-, chalcone-, and alkyl benzylamine-linked xanthone hybrids exhibit multitarget activity suitable for treating complex diseases. Collectively, these findings position xanthone-based hybrids as versatile scaffolds with high translational potential, warranting further preclinical and clinical evaluation to optimize pharmacokinetics, efficacy, and safety for next-generation therapeutics.