ABSTRACT
A dihydroartemisinin-ciprofloxacin hybrid was synthesized and its antiplasmodial activity was evaluated againstthe 3D7 strain of Plasmodium falciparum. It was hypothesized that linking the artemisinin pharmacophore (whichtargets the heme detoxification pathway of the malaria parasite) with the fluoroquinolone scaffold (which targetsplasmodial DNA gyrase enzyme) will produce a hybrid antimalarial compound with enhanced potency. The hybridwas synthesized by esterifying the carboxyl group of ciprofloxacin with the hydroxyl group of dihydroartemisinin; itdisplayed excellent antimalarial activity against the strain of P. falciparum tested with between 3- and 4-fold greateractivity (IC50: 2.99 nM) compared to the reference drugs chloroquine (IC50: 13.003 nM) and dihydroartemisinin alone(IC50: 9.968 nM) against the parasite. The synthesized compound was also tested for its in vitro cytotoxicity and itwas found to be relatively non-cytotoxic (LC50: 50.78 µg/ml) as compared to cyclophosphamide (LC50: 1.08 µg/ml). In silico prediction of the Lipinski properties of the hybrid showed that the compound possesses good drug-likeproperties. The hybrid demonstrated the good activity with minimal toxicity and is, therefore, a potential candidate forfurther exploration in the quest for desperately needed new antimalarial drugs.