Natural and Synthetic Xanthones in the Search for New Antimicrobial Agents: From Structural Diversity and In Vitro Activity to Translational Challenges

Abstract

The global rise of antimicrobial resistance represents a major challenge to public health and highlights the urgent need for the discovery of new antibacterial agents. Xanthones, characterized by a rigid dibenzo-γ-pyrone scaffold, have emerged as promising candidates owing to their broad structural diversity and ability to interact with multiple biological targets. This review provides examples of natural, semisynthetic, and synthetic xanthone derivatives investigated for their antimicrobial potential. Natural xanthones and their structural diversity are first discussed, followed by an analysis of semisynthetic and synthetic derivatives developed to overcome the structural limitations imposed by natural biosynthetic pathways and to improve antimicrobial activity. Particular attention is devoted to structure–activity relationships, including the effects of hydroxylation, methoxylation, alkylation, halogenation, and the position of substituents on antibacterial potency. The review further critically evaluates the factors that may limit the translation of promising in vitro findings into therapeutic applications, including limited mechanistic understanding, physicochemical properties, selectivity, toxicity, and the scarcity of standardized experimental approaches. Collectively, the available evidence supports xanthone derivatives as a valuable and versatile scaffold for the development of new antimicrobial candidates, while also highlighting the substantial work required to advance these compounds toward practical therapeutic applications.