Effects of 13 compounds on activity of globinase and amounts of free amino-acids in Plasmodium berghei

The activity of globinase from Plasmodium berghei was determined by a radiometric method using [3H]globin of mice as substrate. Nine antimalarials (dihydroartemisinin DHQ, artemether AM, chloroquine CQ, primaquine PQ, nitroquine NQ, pyracrini Pyr, changrolin CRL and β-dichroine Di-β), four antineoplastics (10-hydrocamptothecin HC, homoharringtonine HH, methotrexate MTX and cytarabine Ara-C), and FeCl3 were tested on their capacities to inhibit the proteolysis in the above model system. The results showed that AS, Pyr, CQ and CRL exhibited inhibitory effects on the proteolysis at 1, 1, 10 and 10 mmol/L, respectively, but not at the lower concentrations, suggesting that the mode of antimalarial action of these drugs is not by inhibiting the globinase.
Since Fe3+ 1 mmol/L inhibited the proteolysis, the ferri-portion of ferriprotoporphyrin IX (FP) may be responsible for the inhibition of the proteolysis. CQ did not inhibit the proteolysis at 1 mmol/L that was much higher than its effective concentration against malaria parasites, but the binding of CQ to FP might hinder FP sequestration.
HC showed a strong inhibition on the proteolysis, that may be a clue to search for the antimalarials with novel structures.
The levels of free amino-acids in P herghei were not affected by DHQ 33 μmol/L after incubation in vitro at 37 °C for 4 h.