Comprehensive Comparison of the Pharmacological Profiles of Acridine and Acridone Derivatives

Abstract:

Acridine and acridone are important nitrogen-containing heterocyclic scaffolds that have attracted much attention in medicinal chemistry owing to their broad spectrum of biological activities, especially their anticancer potential. Many derivatives, due to their planar aromatic structures, intercalate into DNA and interfere with important cellular processes, such as topoisomerase inhibition, ultimately leading to cell cycle arrest and apoptosis. Furthermore, several recently synthesized derivatives have demonstrated activity towards protein kinases and other molecular targets besides DNA, increasing their therapeutic potential. This review presents a comprehensive comparative study of acridine and acridone scaffolds, covering their chemical structures, mechanisms of action, structure-activity relationships, pharmacological applications, and clinical advancements. Recent advances in the development of these heterocyclic systems are discussed with representative compounds, including derivatives that have been investigated both preclinically and clinically. Current challenges related to selectivity, pharmacokinetic properties, toxicity, and clinical translation are critically evaluated. In conclusion, this review provides a comprehensive summary of the current status of research and future directions in the rational design and optimization of acridine and acridone-based therapeutics for cancer and other diseases.