Emerging Role of Acridine Nucleus in The Treatment of Rare and Neglected Diseases: A Review

Rare and neglected diseases continue to pose significant global health challenges, particularly in resource-limited settings, where therapeutic options remain inadequate. The World Health Organization recognizes neglected tropical diseases and rare disorders as priority areas requiring innovative and cost-effective treatment strategies. In this context, the acridine nucleus has gained renewed attention as a privileged heterocyclic scaffold in medicinal chemistry. Owing to its planar tricyclic structure and strong DNA intercalating properties, acridine derivatives exhibit diverse pharmacological activities, including antimicrobial, antiparasitic, and anticancer effects. Clinically relevant agents such as Quinacrine and Amsacrine highlight the therapeutic versatility of this scaffold. Recent investigations emphasize structure–activity relationship optimization, hybrid molecule development, and drug repurposing approaches to enhance efficacy while minimizing toxicity. This review critically discusses the chemical characteristics, molecular mechanisms, and emerging therapeutic applications of acridine-based compounds in rare and neglected diseases, underscoring their potential as adaptable and promising candidates for addressing unmet medical needs.