State-of-the-art Review on the Antiparasitic Activity of Benzimidazolebased Derivatives: Facing Malaria, Leishmaniasis, and Trypanosomiasis

Abstract

Protozoan parasites represent a significant risk for public health worldwide, afflicting particularly people in more vulnerable categories and cause large morbidity and heavy economic impact. Traditional drugs are limited by their toxicity, low efficacy, route of administration, and cost, reflecting their low priority in global health management. Moreover, the drug resistance phenomenon threatens the positive therapy outcome. This scenario claims the need of addressing more adequate therapies. Among the diverse strategies implemented, the medicinal chemistry efforts have also focused their attention on the benzimidazole nucleus as a promising pharmacophore for the generation of new drug candidates. Hence, the present review provides a global insight into recent progress in benzimidazole-based derivatives drug discovery against important protozoan diseases, such as malaria, leishmaniasis and trypanosomiasis. The more relevant chemical features and structure-activity relationship studies of these molecules are discussed for the purpose of paving the way towards the development of more viable drugs for the treatment of these parasitic infections.

Identification of Innovative Folate Inhibitors Leveraging the Amino Dihydrotriazine Motif from Cycloguanil for Their Potential as Anti-Trypanosoma brucei Agents

“…On the wave of these findings, we considered it interesting to synthesize a novel set of compounds (Table ), the 2-aminotriazino[1,2- a ]benzimidazoles ( 1a– g ), that were obtained through the scaffold hopping manipulation of Cyc, leading to a new tricyclic system where the key amino dihydrotriazine motif of Cyc was integrated with the benzimidazole ring. Noteworthy, benzimidazole is regarded as a “privileged structure” in heterocyclic chemistry due to its association with a wide range of biological activities. , In the field of antiprotozoan agents, it recurs in several examples as the primary unit or meaningful substructure. − …”