Comparison of the in vitro activities of quassinoids with activity against Plasmodium falciparum, anisomycin and some other inhibitors of eukaryotic protein synthesis.
Using the inhibition of incorporation of [3H]hypoxanthine as an index of viability of malaria parasites, it was shown that a chloroquine-sensitive strain of Plasmodium falciparum (T9-96) and a chloroquine-resistant strain (K1) did not differ in their sensitivities to the quassinoids ailanthinone, bruceantin and chaparrin. Similarly, there were no differences between the strains in their sensitivities to the protein synthesis inhibitors anisomycin, deacetylanisomycin, cephalotaxine, homoharringtonine, cycloheximide, puromycin and puromycin aminonucleoside. The IC50 values derived for ailanthinone and bruceantin, cycloheximide, homoharringtonine and puromycin were in the nanomolar range, whereas those for the anisomycins, cephalotaxine and the aminonucleoside of puromycin were micromolar or greater. Those drugs tested which contain an ester moiety (ailanthinone, bruceantin, anisomycin, homoharringtonine) were more active than the related drugs (chaparrin, deacetylanisomycin, cephalotaxine) that do not. Cross-resistance to inhibitors of protein synthesis appeared not to accompany resistance to chloroquine.
Ekong
R M
RM
Department of Medical Parasitology, London School of Hygiene and Tropical Medicine, U.K.
Kirby
G C
GC
Patel
G
G
Phillipson
J D
JD
Warhurst
D C
DC
D000818:Animals; D000841:Anisomycin / Q000494:pharmacology*; D002738:Chloroquine / Q000494:pharmacology; D010963:Plasmodium falciparum / Q000187:drug effects*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D011691:Puromycin / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D011500:Protein Synthesis Inhibitors; D011759:Pyrrolidines; D011691:Puromycin; D000841:Anisomycin; D002738:Chloroquine