A Dihydroartemisinin-Ciprofloxacin hybrid was synthesized and its antiplasmodial activity evaluated against the 3D7 strain of Plasmodium falciparum. It was hypothesized that linking the Artemisinin pharmacophore (which targets the heme detoxification pathway of the malaria parasite) with the Fluoroquinolone scaffold (which targets plasmodial DNA Gyrase enzyme) will produce a hybrid antimalarial compound with enhanced potency. The hybrid was synthesized by esterifying the carboxyl group of Ciprofloxacin with the hydroxyl group of dihydroartemisinin; it displayed excellent antimalarial activity against the strain of P. falciparum tested with between 3-4 fold greater activity (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 it was 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 like properties. The hybrid demonstrated good activity with minimal toxicity and is therefore a potential candidate for further exploration in the quest for desperately needed new antimalarial drugs.
Key words: Gyrase inhibition, Dihydroartemisinin, Ciprofloxacin, Malaria, Plasmodium
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