Antimalarial agents. III. Mechanism of action of artesunate against Plasmodium berghei infection.

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Abstract
The antimalarial agent, artesunate has been observed to suppress the infection growth rate of Plasmodium berghei in CF1 mouse red blood cells. The inhibition of growth was due to a number of biochemical mechanisms. Deoxyribonucleic acid (DNA) synthesis in the Plasmodium berghei was inhibited significantly by the drug with marginal inhibition of protein synthesis. The inhibition of DNA synthesis seemed to be due to a block of purine synthesis at the regulatory enzyme site of inosine monophosphate (IMP) dehydrogenase. Whereas there was no evidence to demonstrate that the drug alkylated nucleotide bases or caused cross linking of DNA strands of the plasmodium, the drug did appear to cause non-specific binding to bases that interfered with template activity. There was marked inhibition of messenger ribonucleic acid (mRNA) polymerase activity with moderate inhibition of DNA polymerase activity. The drug caused significant reduction of basal oxygen consumption of Plasmodium berghei with a significant inhibition of succinic acid dehydrogenase activity. The drug interacted with reduced nicotinamide adenine dinucleotide (NADH), suggesting the possibility that artesunate may interfere with energy required for cell growth.