Is structural hybridization invoking new dimensions for antimalarial drug discovery research?

Despite effective prevention methods, malaria is a devastating, persistent infection caused by protozoal parasites that result in nearly half a million fatalities annually. Any progress made thus far in the eradication of the disease is jeopardized by the expansion of malaria parasites that have evolved to become resistant to a wide range of drugs, including first-line therapy. To surmount this significant obstacle, it is necessary to develop newly synthesized drugs with multiple modes of action that may have a novel target in various stages of Plasmodium parasite development and this is made possible by the hybridization concept. Hybridization is the combination of at least two diverse pharmacophore units with some linkers bringing about a single molecule with a diverse mode of action. It intensifies a drug's physiological and chemical characteristics, such as absorption, cellular target contact, metabolism, excretion, distribution, and toxicity. This review article outlines the currently published most potent hybrid drugs against the Plasmodium species.