Figure 1

Inhibitory effect of anti-malarial drugs on ABC transport activity. The inhibitory effect of 100 μM of CQ, Q, ART, MQ, L, ATO, DHA and PG on ABC transporter activity was assessed. Transport was measured in pmol/mg protein/min and expressed as percentage of solvent controls, which represent 100% transport. Bars with * are significantly different from solvent controls, p < 0.05. A P-gp-mediated transport of NMQ was significantly inhibited by CQ, Q, MQ and PG, and increased by ART and DHA. B BCRP-mediated transport of E1S was significantly inhibited by all compounds, most pronounced inhibitors were MQ and ATO. C BSEP-mediated transport of TCA was significantly inhibited by ATO, but not by the other anti-malarials. Induction of transport was observed for CQ, ART and DHA. D-G MRP1-4-mediated E217βG transport. MQ significantly inhibited MRP1 and MRP3 transport activity. Furthermore, induction of MRP1 mediated transport was found for ATO, which, together with ART, also stimulated MRP2 transport activity. MRP3 mediated transport was stimulated by both ART and DHA. Inhibition larger than 66.7% was found for Q and MQ on P-gp transport, as well as MQ, ATO and PG on BCRP transport activity (highlighted bars).