Evaluation of anti-malarial potency of new pyrazole-hydrazine coupled to Schiff base derivatives

Background: The search for pharmacologically effective agents among molecules bearing multiple functionalities is commonly practiced. In continuation of the search for new anti-malarial agents, new pyrazole-hydrazine coupled Schiff-base derivatives previously synthesized were screened for anti-malarial property.

Methods: Here, in vivo prophylactic and curative activities of the compounds were assessed while their binding affinity for falcipain-2, a crucial enzyme in Plasmodium survival, was done using computational techniques.

Results: The two derivatives (BepINH and BepBeH) respectively led to a significant (p < 0.05) reduction in parasitaemia count (0.76 ± 1.11 and 0.79 ± 1.19) at day 3 post-treatment relative to the negative control (16.37 ± 1.25). For the prophylactic study, it was observed that the highest parasitaemia suppression level of 95.35% and 95.17% for BepINH and BepBeH at 15 mg/kg was slightly comparable to that obtained for ACT-Lonart (99.38%). In addition, their haematological profiles indicate that they are potentially beneficial in suppressing haemolytic damage to RBC, thereby protecting the body against infection-induced anaemia. Docking calculations on the derivatives toward the Plasmodium falciparum falcipain-2 revealed that they favourably interacted with a binding affinity higher than that of a known cocrystallized inhibitor.

Conclusion: This study confirms the relevance of multi-functional molecules in the search for new and effective anti-plasmodial agent and lay the foundation for further development of these compound series to potent anti-plasmodial agent that interacts with falcipain-2.