Purine derivatives as potent anticancer agents: a comprehensive review

Cancer remains an incessantly rising cause of mortality worldwide, tempting millions of lives each year and posing a significant global health challenge. Available treatment modalities, including chemotherapy, have been associated with limited scope with severe side effects and complexities, underscoring the imperative need for more efficient and safe curative strategies. In this context, the rational design of multitargeted anticancer agents has gained momentum, aiming to enhance therapeutic outcomes while reducing systemic toxicity. The purine scaffold, a core structural motif found in essential biomolecules, such as deoxyribonucleic acid (DNA), ribonucleic acid (RNA), adenosine triphosphate (ATP), and nicotinamide adenine dinucleotide (NAD), has emerged as a promising pharmacophore in anticancer drug discovery. Notably, several synthetic purine analogues have received clinical approval owing to their potent anticancer activity, particularly when integrated with diverse heterocyclic frameworks. This review comprehensively summarizes the advances made over the past decade in the development of purine-based hybrid molecules, highlighting their mechanistic roles in overcoming drug resistance and targeting multiple oncogenic pathways. The insights presented herein underscore the versatility and therapeutic relevance of purine-based scaffolds and aim to guide future efforts in the rational design and development of drug-resistant and safer anticancer agents.