TABLE 1

Reference compounds evaluated in three-point 10-fold dilution series on P. cynomolgi liver stages

Compound nameActivity againsta:
Hypnozoite formsSchizonts
Amodiaquineb
Artesunateb
Dihydroartimisinb
Lumefantrineb
Piperaquineb
Chloroquineb±
Doxycyclineb±±
Mefloquineb±+
Proguanilb±+
Atovaquonec+++
Cycloheximided+++
Primaquinee++++++
NPC-1161Bf++++++
Tafenoquinef+++++
Bulaquinef++++++
  • a Activities of compounds (reduction of parasite counts at 10 μM) are represented as follows: −, 0 to 10%; ±, 10 to 20%; +, 20 to 70%; ++, 70 to 90%; +++, >90%. Of the nonaminoquinoline antimalarials, only atovaquone reduced the number of developing liver stage parasites by more than 90%. The nonspecific protein synthesis inhibitor cycloheximide had a minor effect on the number of small and large liver stage parasites at the highest concentration tested. All 8-aminoquinolines tested were active in the P. cynomolgi in vitro assay, efficiently killing both schizonts and hypnozoite forms.

  • b Reference compound had known blood stage activity.

  • c Reference compound had known blood and liver stage activity.

  • d Reference compound is a known protein synthesis inhibitor.

  • e Reference compound is an 8-aminoquinoline, used as a radical cure, active against gametocytes and liver stages (including hypnozoites).

  • f Reference compound is an 8-aminoquinoline.