Structural Insights and Biological Activities of Salicylanilide-based Compounds: A Comprehensive Review

Abstract: Salicylanilide-based compounds represent a versatile class of bioactive molecules with broad therapeutic potential. Originally developed as anthelmintic agents, these compounds have subsequently attracted considerable attention due to their diverse pharmacological activities, including antimicrobial, anticancer, anti-osteoclastogenic, anti-obesity, cardiovascular, and neuroprotective effects. In recent years, extensive medicinal chemistry efforts have focused on optimizing the salicylanilide scaffold to improve biological activity, target selectivity, and pharmacokinetic properties. This review provides a comprehensive overview of the therapeutic applications of salicylanilide derivatives, emphasizing recent advances in their medicinal chemistry, mechanisms of action, and structure–activity relationships (SARs). Analysis of available SAR data reveals several recurring trends across different therapeutic areas. Biological activity is frequently enhanced by electronwithdrawing substituents on the anilide ring, while the phenolic hydroxyl group often plays a critical role in target engagement, although its importance may vary depending on the pharmacological application. In addition, strategic scaffold modifications, including carbamate and thiocarbamate derivatization, prodrug approaches, heterocycle incorporation, and ring-fused analogues, have been successfully employed to improve potency, selectivity, solubility, and bioavailability. Collectively, the available evidence highlights the salicylanilide scaffold as a promising platform for the development of novel therapeutics. The SAR insights summarized in this review provide a valuable framework for the rational design and optimization of next-generation salicylanilide-based drug candidates and support further in vivo and clinical investigations of this scaffold.