Tetraoxanes as inhibitors of Apicomplexan parasites Plasmodium falciparum and Toxoplasma gondii and anti-cancer molecules

Dejan Opsenica, Jelena Radivojević, Ivana Matić, Tijana Štajner, Slavica Knežević-Ušaj, Olgica Djurković-Djaković, Bogdan Aleksandar Šolaja


New cyclohexylidene 1,2,4,5-tetraoxanes with polar guanidine and urea based groups were synthetized and evaluated for antimalarial activity against chloroquine resistant and susceptible Plasmodium falciparum strains. Derivatives showed moderate nM range antimalarial activities and low cytotoxicity. N-phenyl-urea derivative 24 exhibited best resistant indices (RIW2 = 0.44, RITM91C235 =  0.80), and was not toxic against human normal peripheral blood mononuclear cells (IC50 > 200 μM). Seven derivatives were tested in vitro against four human cancer cell lines and they demonstrated high selectivity toward leukemia K562 cells. One compound, derivative 21 with a primary amino-group, was the first tetraoxane tested in vivo against Toxoplasma gondii as another Apicomplexan parasite. Subcutaneous administration at a dose of 10 mg/kg/day for 8 days allowed survival of 20 % of infected mice, thus demonstrating the high potential of tetraoxanes for the treatment of Apicomplexan parasites.


antimalarials; antiparasitic; peroxides; cancer; cytotoxicity

DOI: https://doi.org/10.2298/JSC150430063O

Copyright (c) 2015 Journal of the Serbian Chemical Society - J. Serb. Chem. Soc.

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