In vitro and in vivo antiplasmodial activity of a synthetic dihydroartemisinin-eosin B hybrid.

With the inexorable prevalence and spread of drug-resistant malaria strains, many efforts have been made to find alternative chemotherapeutic agents. In this regard, scientists have developed the concept of hybridization of two or more active pharmacophores into a single chemical compound, resulting in "antimalarial hybrids." The aim of this study was planned based on the highly synergistic effect of the physical hybrid of dihydroartemisinin (DHA) with eosin B (EB). Therefore, a chemical hybrid of the two compounds (DHA-EB) was synthesized, and its antimalarial activity was investigated in vitro and in vivo. The drug hybrid was fabricated through a propionyl ester linker between DHA and EB. The antiplasmodial activity of the new hybrid was tested in vitro on the blood stages of Plasmodium falciparum (chloroquine-sensitive, 3D7 strain) and also evaluated in vivo by Peters' standard test in mice infected with Plasmodium berghei. The hybrid compound was also assessed for in vivo toxicity. Among all the compounds studied, a DHA-EB hybrid showed an appropriate inhibition percentage (53%) was at a very low dose (0.65 nM). The highest in vivo antimalarial activity until the 9 ^th day was related to DHA-EB in a low dose (0.5 mg/kg). Also, the most survival rate was observed in the test group of hybrid compound at a dose of 1.5 mg/kg for 22 days. No external changes were identified in the toxicity assay. The weight of internal organs of treated animals and that of controls indicated nontoxicity of DHA-EB even after 60 days of consumption. In vitro and in vivo studies substantiated that DHA-EB hybrid has the potential for developing as a safe antimalarial drug.
(© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)