Synthesis, Characterization, and Antiplasmodial Evaluation of Novel 2-Pyrazoline Carboxamide Derivatives Against Plasmodium berghei in Mice

Malaria, caused by Plasmodium species, remains a global health challenge, exacerbated by drug resistance, necessitating novel therapeutic agents. Pyrazoline derivatives have shown promise as antimalarial candidates due to their heterocyclic structure and pharmacological versatility. Two novel 2-pyrazoline carboxamide derivatives, P5 and P13, were synthesized via a base-catalyzed one-pot reaction using substituted acetophenones, benzaldehydes, and semicarbazide in ethanol. Compounds were characterized using FT-IR, ¹H NMR, and ¹³C NMR. Acute oral toxicity was assessed in mice per OECD Test No. 423, and antiplasmodial activity was evaluated against Plasmodium berghei in a curative test. Mice were treated with 25, 50, and 100 mg/kg of P5 and P13, with chloroquine (5 mg/kg) as the positive control. Parasitaemia suppression was calculated, and data analyzed using ANOVA with Dunnett’s post hoc test. P5 and P13 were synthesized with yields of 75.6% and 87.3% respectively and spectroscopic data confirmed their pyrazoline structures. They exhibited no toxicity up to 5000 mg/kg. Both compounds significantly reduced parasitaemia in a dose-dependent manner, with P13 achieving 71.43% chemo suppression and P5 61.52% at 100 mg/kg, compared to chloroquine’s 93.70%. P5 and P13 demonstrate promising antiplasmodial activity and safety, with P13 showing superior efficacy, suggesting their potential as novel antimalarial agents warranting further development.