Inhibition of nitric oxide-dependent activation of soluble guanylyl cyclase by the antimalarial drug, artemisinin

Abstract

The influence of artemisinin on the activity of human platelet soluble guanylyl cyclase was investigated. Artemisinin (0.1–100 μM) had no effect on the basal activity of the enzyme. Artemisinin inhibited in a concentration-dependent manner the sodium nitroprusside-induced activation of human platelet guanylyl cyclase with an IC 50 value 5.6 μM. Artemisinin (10 μM) also inhibited (by 71±4.0%) the activation of the enzyme by the thiol-dependent nitric oxide (NO) donor, the derivative of furoxan, 3,4-dicyano-1,2,5-oxadiazole 2-oxide (10 μM), but did not influence the stimulation of soluble guanylyl cyclase by protoporphyrin 1X. Inhibition of guanylyl cyclase activation by NO donors but not by protoporphyrin 1X represents a possible additional mechanism of the pharmacological action of this drug.