Recent Advancement in Pyrazole Derivatives as Antimalarial Agents and their SAR Study

Malaria is caused by protozoan parasites and is a significant contributor to global mortality and morbidity. The main reasons for the resurgence of malaria are the emergence of drug-resistant strains of the parasite and the ineffectiveness of current treatment. Pyrazole-based drugs play a crucial role in medicinal chemistry due to their diverse pharmacological properties. The pyrazole structure, a five-membered ring with two nitrogen atoms, is a key pharmacophore in various therapeutic agents. Numerous derivatives of pyrazole scaffold exhibited a wide range of pharmacological activity such as analgesics, antiinflammatory, antioxidant, antimicrobial, antidiabetic, anticancer, antiviral, antifungal, and antithrombotic activities. These drugs provide numerous opportunities for enhancing antimalarial agents by targeting various critical receptors. Various pyrazole derivatives have been reported to inhibit enzymes, receptors, and other targets to manage malaria. These derivatives inhibited parasite through various mechanisms such as falcipain, dihydrofolate redcutase, dihydroorotate dehydrogenase, lactate dehydrogenase, protein kinase, calcium dependent protein kinase, glycogen synthase kinase, and histo aspartic protease. Currently, researchers are developing new pyrazole-based derivatives, often in combination with other moieties, for improved malaria treatment. This review highlights the recent therapeutic advancements of pyrazole, including its structure-activity relationship, molecular docking, commercial drug availability, and a summary of recent research publications, all of which collectively assist scientists in developing effective drugs with desired pharmacological activities.