Exploring the Recent Pioneering Developments of Small Molecules in Antimalarial Drug Armamentarium: A Chemistry...

Malaria is a very destructive and lethal parasitic disease that causes significant mortality worldwide, resulting in the loss of millions of lives annually. It is an infectious disease transmitted by mosquitoes, which is caused by different species of the parasite protozoan belonging to the genus Plasmodium. The uncontrolled intake of antimalarial drugs often employed in clinical settings has resulted in the emergence of numerous strains of plasmodium that are resistant to these drugs, including multidrug-resistant strains. This resistance significantly diminishes the effectiveness of many primary drugs used in the treatment of malaria. Hence, there is an urgent need for developing unique classes of antimalarial drugs that function with distinct mechanisms of action. In this context, the design and development of hybrid compounds that combine pharmacophoric properties from different lead molecules into a single unit gives a unique perspective towards further development of malaria drugs in the next generation. In recent years, the field of medicinal chemistry has made significant efforts resulting in the discovery and synthesis of numerous small novel compounds that exhibit potent antimalarial properties, while also demonstrating reduced toxicity and desirable efficacy. In light of this, we have reviewed the progress of hybrid antimalarial agents from 2021 up to the present. This manuscript presents a comprehensive overview of the latest advancements in the medicinal chemistry pertaining to small molecules, with a specific focus on their potential as antimalarial agents. As possible antimalarial drugs that might target both the dual stage and multi-stage stages of the parasite life cycle, these small hybrid molecules have been studied. This review explores a variety of physiologically active compounds that have been described in the literature in order to lay a strong foundation for the logical design and eventual identification of antimalarial drugs based on lead frameworks.