Synergism between pyronaridine and retinol in Plasmodium falciparum in vitro

Pyronaridine, a naphthyridine derivative and Mannich base, is a highly active blood schizontocide and currently being explored as partner in artemisinin-based combination therapy (ACT). In this study, carried out 2008 in Mae Sot, Thailand, the activity of pyronaridine was found to be compromised, obviously as the result of mono-therapy in an adjacent area. The pyronaridine sensitivity and the interaction between pyronaridine and retinol at concentrations corresponding to the 50th, 65th and 80th percentile of the physiological retinol levels in healthy adults were assessed in 38 fresh isolates of P. falciparum. The mean IC50, IC90 and IC99 values for pyronaridine were 12.7, 201.4 and 3084.2 nM, those for pyronaridine + retinol "low" 1.2, 14.0 and 102.6 nM, those for pyronaridine + retinol "medium" 0.6, 7.4 and 54.8 nM, and those for pyronaridine + retinol "high" 0.9, 8.2 and 47.8 nM. There was significant evidence of strong synergism between pyronaridine and retinol against P. falciparum.