Anti-malarial effect of semi-synthetic drug amitozyn

Malaria caused by Plasmodium falciparum is the most virulent form of malaria, leading to approximately a half million deaths per year. Chemotherapy continues to be a key approach in malaria prevention and treatment. Due to widespread parasite drug resistance, identification and development of new anti-malarial compounds remains an important task of malarial parasitology. The semi-synthetic drug amitozyn, obtained through alkylation of major celandine (Chelidonium majus) alkaloids with N,N′N′-triethylenethiophosphoramide (ThioTEPA), is a widely used Eastern European folk medicine for the treatment of various tumours. However, its anti-malarial effect has never been studied.

Obtained results demonstrate that amitozyn effectively inhibits the growth of blood-stage parasites with IC₅₀ 9.6 ± 2, 11.3 ± 2.8 and 10.8 ± 1.8 μg/mL using CS2, 3G8 and NF54 parasite lines, respectively. The median IC₅₀ for 14 tested human cell lines was 33–152 μg/mL. Treatment of uninfected red blood cells with a high dose of amitozyn (500 μg/mL) did not change cell morphology, demonstrating its non-toxicity for erythrocytes. The synergistic impact of the amitozyn/chloroquine combination was observed at growth inhibition levels of 10–80 %, while demonstrating a nearly additive effect at a growth inhibition level of 90 %. The combination of amitozyn with pyrimethamine has a synergistic effect at growth inhibition levels of 10–70 % and a nearly additive effect at a growth inhibition level of 90 %. The synergistic anti-malarial effect of the amitozyn/artemisinin combination was observed at growth inhibition levels of 10–40 % and a nearly additive effect at growth inhibition levels of 50–90 %.

These in vitro results suggest that the semi-synthetic drug amitozyn, typically used for the treatment of tumours, is a potential anti-malarial candidate and warrants more detailed laboratory and pre-clinical investigations.