Antiplasmodial effect of benzimidazole-pyrazole derivative against Plasmodium berghei infection in mice model

Malaria is a vector-borne and blood-borne disease substantially contributing to morbidity and mortality worldwide for many years, especially in developing countries, causing a serious threat to public health. The growing resistance of the Plasmodium parasite to existing antimalarials highlights the urgent need for novel drugs. The present study aimed to investigate the antiplasmodial effect of three doses of 2-((1H-benzo[d]imidazole-2-yl)thio)-1-(3,5-diphenyl-1H-pyrazol-1-yl)ethenone (3a) on Plasmodium berghei induced malaria in mice using chloroquine as a reference drug. Mice were observed for morphological and behavioral changes, as well as hematological and biochemical analysis. Liver and spleen were subjected to histopathology, antioxidant assays, immunohistochemical analysis, and polymerase chain reaction. Furthermore, molecular docking was performed to assess antimalarial protein targets. The study provides compelling evidence that 3a demonstrated dose-dependent reduction in parasitemia, restoration of hematological and biochemical parameters with 800 μg/kg of 3a, antioxidant potential via decreasing oxidative stress markers and enhancing antioxidant markers. Furthermore, it also supports the anti-inflammatory property of compound via reducing levels of proinflammatory cytokines in immunohistochemistry and polymerase chain reaction. Docking study indicates that binding affinity of 3a with P. falciparum proteins is even better than that of chloroquine especially with P. falciparum plasmepsins. Hence 3a offers a promising alternative candidate in search for new antimalarial agents.

Antimalarials; Benzimidazole-pyrazole derivative; Docking; Immunohistochemistry; In vivo; Inflammation; Oxidative stress; Parasitemia; Plasmodium berghei.