Plasmodium berghei K173: Selection of resistance to naphthoquine in a mouse model

Naphthoquine (NQ), as a component of ARCO® which composed of NQ and artemisinin, is a new 4-aminoquinoline antimalarial synthesized by our institute. Here, a naphthoquine-resistant line of rodent malaria parasite was selected through exposing Plasmodium berghei Keyberg 173 strain to progressively increased drug pressure. The selected strain showed a more than 200-fold decreased susceptibility to NQ with a stable resistance phenotype after 10 serial passages without drug pressure or when cryopreserved over a period of 12 months. In a cross-resistance assay, the susceptibility of NQ-resistant parasites to chloroquine was decreased by 14.5-fold. These findings imply NQ-resistant parasites might be selected by long-term usage of NQ in epidemic areas and the efficacy of NQ or ARCO® in chloroquine-resistant Plasmodium falciparum epidemic areas should be monitored closely.

Research highlights► High level of stable naphthoquine resistant strain (I90 = 200.3) can be selected in Plasmodium berghei. ► Under naphthoquine pressure, there is no strong indication of resistance in both I50 and I90 until the 20th passage. ► Evaluation of cross-resistance patterns revealed a significant 14.5-fold decrease in the activity of chloroquine against naphthoquine resistant parasite line.