Antimalarial Activity of Indole Derivatives: A Comprehensive Review

Malaria remains a major global health challenge, particularly in tropical and subtropical regions, with increasing resistance to existing antimalarial drugs threatening current control strategies. The continuous emergence of resistance to classical antimalarials such as chloroquine, sulfadoxine–pyrimethamine, and even artemisinin-based combination therapies has intensified the search for novel chemotherapeutic agents. Among various heterocyclic scaffolds explored in medicinal chemistry, indole and its derivatives have gained significant attention due to their structural versatility, biological relevance, and presence in numerous bioactive natural products. This review provides a comprehensive overview of the antimalarial potential of indole derivatives, covering their chemical characteristics, natural and synthetic sources, mechanisms of action, structure–activity relationships, recent advances, challenges, and future prospects in antimalarial drug discovery.