Antiparasitic activity of alkaloids from plant species of Papua New Guinea and Australia.
New drugs are needed to help overcome the increasing problem of drug resistance in parasites that cause diseases such as malaria and trypanosomiasis. In this study, alkaloid compounds isolated from extracts of the plants Flindersia amboinensis, Stephania zippeliana and Voacanga papuana from Papua New Guinea and Flindersia acuminata from Australia were examined for their antiparasitic activity against Plasmodium falciparum strains and Trypanosoma brucei brucei as well as their cytotoxicity against the mammalian cell lines HEK 293 and HeLa. The most active compound, dimethylisoborreverine (DMIB), showed submicromolar activity, with 50% inhibitory concentration (IC(50)) values between 20 nM and 810 nM both against drug-sensitive and drug-resistant P. falciparum strains, along with moderate selectivity against T. b. brucei and mammalian cells. Stage specificity studies revealed that P. falciparum trophozoite-stage parasites were more susceptible to DMIB than ring- or schizont-stage parasites. DMIB-treated trophozoites showed changes in food vacuole morphology, with an apparent reduction in haemozoin formation that does not appear to be inhibited via the direct binding of haem. These findings suggest a potential for indole alkaloids from Flindersia spp. as new antiparasitic agents.
Fernandez
Liza S
LS
Eskitis Institute for Cell and Molecular Therapies, Griffith University, Brisbane, Australia.
Sykes
Melissa L
ML
Andrews
Katherine T
KT
Avery
Vicky M
VM
D000470:Alkaloids / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D000977:Antiparasitic Agents / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D001315:Australia; D002460:Cell Line; D004847:Epithelial Cells / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D010219:Papua New Guinea; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D010963:Plasmodium falciparum / Q000187:drug effects*; D027821:Rutaceae / Q000737:chemistry; D031607:Stephania / Q000737:chemistry; D014346:Trypanosoma brucei brucei / Q000187:drug effects*; D036902:Voacanga / Q000737:chemistry
D000470:Alkaloids; D000977:Antiparasitic Agents; D010936:Plant Extracts