Exploring Natural Coumarins in Antiprotozoal Drug Discovery: A Comprehensive Review

ABSTRACT Parasitic diseases continue to be a major public health burden, particularly in low‐ and middle‐income countries. With the emergence of drug‐resistant strains and limitations of current therapies, there is a growing interest in natural products as alternative treatment options. Coumarins, a diverse class of plant‐derived secondary metabolites, have shown significant potential as antiparasitic agents. This review compiles and critically analyzes the antiparasitic activities of natural coumarins against a wide range of protozoan parasites, including Plasmodium , Leishmania , Trypanosoma , and Entamoeba histolytica . The pharmacological effects of coumarins are attributed to their ability to interfere with parasite metabolism, disrupt mitochondrial function, inhibit key enzymes, and modulate host immune responses. Several coumarin derivatives have demonstrated potent in vitro and in vivo efficacy with good selectivity toward the parasite. Structure–activity relationship studies further highlight the importance of specific substitutions on the coumarin core in enhancing biological activity. Although challenges such as low solubility and bioavailability remain, recent advancements in formulation and molecular design offer promising solutions. Overall, coumarins represent a valuable chemical scaffold with significant promise for the development of novel antiparasitic therapies.