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

Abstract

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.

Synthesis, antileishmanial, antimalarial evaluation and molecular docking study of some hydrazine-coupled pyrazole derivatives

“…In this regard, Bekhit and coworkers [22] successfully synthesized different hydrazine-coupled pyrazole derivatives (I-VI) with potent antimalarial activities having high percent suppression (94. 19 to 97.67%) against Plasmodium berghei infected mice at a dose of 48.4 µM/kg per day. In addition, the compounds (Fig.…”

“…antioxidant activities [18], etc. Moreover, hydrazine-coupled pyrazole derivatives are shown to have promising antimalarial and antileishmanial activities [19][20][21]. In this regard, Bekhit and coworkers [22] successfully synthesized different hydrazine-coupled pyrazole derivatives (I-VI) with potent antimalarial activities having high percent suppression (94.…”

Small Schiff Base Molecules—A Possible Strategy to Combat Biofilm-Related Infections

“…Schiff bases have numerous applications including coordination chemistry [23], catalysis [24], chemosensors [25] and intermediates in synthesis [26,27]. They also exhibit a variety of biological applications: antibacterial [28][29][30][31][32][33][34], antifungal [34][35][36], antiviral [37,38], antimalarial [39,40], antituberculosis [41][42][43], anthelmintic [44,45], urease inhibitors [46][47][48], anticancer [49][50][51], antidyslipidemic [52], antidiabetic [53,54], antidepressant Schiff bases are compounds with the structure R'N=CR 2 (R' ̸ = H) [22], traditionally formed in the reaction of alkyl/aryl aldehydes or ketones with primary amines [23]. Many considered them to be synonymous with azomethines (RN=CR 2 , R ̸ = H), both being a particular case of imines (RN=CR 2 , R = H, hydrocarbonyl) [22].…”

Synthesis, antileishmanial, antimalarial evaluation and molecular docking study of some hydrazine-coupled pyrazole derivatives

“…Pyrazoles are a class of bioactive compounds with diverse pharmacological effects such as anticancer [ 18 , 19 ], antiviral [ 20 , 21 ], antifungal [ 22 ], antibacterial [ 23 ], anti-inflammatory [ 24 ], antioxidant activities [ 25 ]. Moreover, hydrazine-coupled pyrazole derivatives are shown to have promising antimalarial and antileishmanial activities [ 26 – 28 ]. In this regard, Bekhit and coworkers [ 29 ] successfully synthesized different hydrazine-coupled pyrazole derivatives ( I-VI ) with potent antimalarial activities having high percent suppression (94.19 to 97.67%) against mice infected with Plasmodium berghei at a dose of 48.4 µM/kg per day.…”