An updated survey on the recent advancement of antimalarial molecules: synthetic methodologies and SAR studies

An ongoing escalation in malaria cases is a critical global health issue and also a leading source of increased mortality rates. Infected mosquitos spread the Plasmodium parasite-based disease,. Recent advancements in antimalarial drug discovery have focused on developing novel molecules with unique mechanisms of action to combat this growing resistance. This review focuses on the latest findings in synthesizing hybrid antimalarial compounds, which combine different pharmacophores to enhance therapeutic efficacy, resulting in compounds that exhibit potent action against both resistant/sensitive strains of chloroquine, quinine, and artemisinin. Notably, the incorporation of diverse scaffolds such as 1,2,4-trioxanes, halogenated quinolines, pyrazoline, and sulfonamides has led to promising candidates that not only demonstrate high potency but also favorable pharmacokinetic profiles for drug development, the exploration of novel targets. This review highlights the progress (2019-2024) made in identifying and synthesizing hybrid antimalarial molecules while addressing existing challenges in the field.