Protease inhibitors and antimalarial effects
Scheibel, L.W.; Bueding, E.; Fish, W.R.; Hawkins, J.T.
Progress in Clinical and Biological Research 155: 131-142
1984
ISSN/ISBN: 0361-7742 PMID: 6382312 Document Number: 224748
Several protease inhibitors, cyclosporin A (CSA) and analogues of CSA were shown to be potent inhibitors of the in vitro growth of Plasmodium falciparum (chloroquine-resistant FCB/K+ strain). The antimalarial activity had approximately the same rank order as antischistosomal haemoglobinase activity, the most potent being the leucine analogue Ep-475. Pepstatin and antipain had no activity against P. falciparum. Studies on the effects of various protease inhibitors on haemoglobinase activity of P. falciparum at pH 3.85, 5.0 and 7.0 showed that Qinghaosu at the very high concentration of 1.4 x 10-3 M and CSA were inactive at all pH values. It is considered that if the antimalarial activity of these 2 compounds is related to haemoglobinase inhibition, then both compounds may be metabolized either in the parasite or in the red cell to a metabolite which is a protease inhibitor.