Malaria-associated morbidity and mortality pose a major threat to public health globally, contributing to 245 million cases in 2020, 247 million in 2021, and 249 million in 2022 (with the highest cases reported in Africa), resulting in an estimated death of 608,000 individuals [1]. Since malaria is endemic to tropical and underdeveloped regions, non-availability and costly medication are among the major factors causing mortality among these impoverished communities [2].

Despite many potential candidates underway in the development of an effective and accessible vaccine, the prospect of it being successful is faced with limitations like complexity in the life cycle of Plasmodium spp. and high cost of vaccine [3]. Plasmodium falciparum is the most lethal among all parasite species that cause malaria in humans [4].

Over the past years, P. falciparum has shown resistance to most antimalarials, including artemisinin, quinine, chloroquine, sulfadoxine-pyrimethamine [5], mefloquine, and piperaquine [4], leading to compromised efficacy [6,7]. The resistance to antimalarial drugs has become a major public health threat potentially resulting from widespread and irrational use of antimalarials, uncontrolled and mass dosage administration, which leads to repeated exposure of the parasite to subtherapeutic levels of the drug in blood plasma further contributing to genetic mutations in the parasite [8]. As a result of treatment failure to artemisinin monotherapy and to deal with multi-drug resistant parasite, Artemisinin-based Combination Therapies (ACTs) are recommended as the first-line treatment of malaria by WHO but their restricted availability, undesirable adverse effects such as severe hepatoxocity [9], relatively high cost and reported resistance in some Asian regions and in East Africa [10] has become a major obstacle in the treatment and eradication of disease.

Due to the abovementioned limitations, the search for novel effective compounds having structural diversity has become a central objective in the context of malaria eradication [11]. The use of combination therapies and hybrid compounds (two or more pharmacophores) is one of the best approaches to overcoming resistance. The importance of benzimidazole and pyrazole nuclei in medical literal cannot be overemphasized due to their medicinal properties, including but not limited to antimicrobial, anti-inflammatory, anti-viral, analgesic, anti-alzheimer, anti-ulcer, anti-cancer and anti-diabetic [12]. Benzimidazole derivatives are reported to treat mitochondrial dysfunction in Alzheimer's disease [13], effective in the treatment of diabetes mellitus [14], psychoactive and neurotropic in nature [15], and possess anticoagulant properties [16]. Additionally, pyrazole derivatives have anti-microbial, analgesic, anti-tumor, anticonvulsant, anti-viral, anti-diabetic, anti-pyretic [12] and anti-malarial properties [17,18].

In the present study, 2-((1H-benzo[d]imidazole-2-yl)thio)-1-(3,5-diphenyl-1H-pyrazol-1-yl)ethenone is a synthetic hybrid of benzimidazole and pyrazole moieties abbreviated as 3a. The structure of 3a is shown in Fig. 1. It is previously been reported as anti-ulcer [19]. This study investigates the in vivo antiplasmodial potential of 3a in P. berghei infected mice based on the previously reported antimicrobial and antimalarial potential of imidazoles and pyrazole derivatives.