Tetraoxanes as inhibitors of apicomplexan parasites Plasmodium falciparum and Toxoplasma gondii growth and anti-cancer molecules
2015
Authors
Opsenica, Dejan M.Radivojević, Jelena
Matić, Ivana Z.
Štajner, Tijana
Knezevic-Usaj, Slavica
Đurković-Đaković, Olgica
Šolaja, Bogdan A.
Article (Published version)
Metadata
Show full item recordAbstract
New cyclohexylidene 1,2,4,5-tetraoxanes with polar guanidine and urea based groups were synthesized and evaluated for their antimalarial activity against chloroquine resistant and susceptible Plasmodium falciparum strains. The derivatives showed moderate, nM range antimalarial activities and low cytotoxicity. The N-phenylurea derivative 24 exhibited the best resistance indices (RIW2 = 0.44, RITM91C235 = 0.80) and was not toxic against human normal peripheral blood mononuclear cells (IC50 gt 200 mu M). Seven derivatives were tested in vitro against four human cancer cell lines and they demonstrated high selectivity toward leukaemia 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(-1) day(-1) for 8 days allowed the survival of 20 % of infected mice, thus demonstrating the high potential of tetraoxanes for the treatment ...of apicomplexan parasites.
Keywords:
antimalarials / antiparasitic / peroxides / cancer / cytotoxicitySource:
Journal of the Serbian Chemical Society, 2015, 80, 11, 1339-Publisher:
- Serbian Chemical Soc, Belgrade
Funding / projects:
- The synthesis of aminoquinoline-based antimalarials and botulinum neurotoxin A inhibitors (RS-172008)
- Biological response modifiers in physiological and pathological conditions (RS-175011)
DOI: 10.2298/JSC150430063O
ISSN: 0352-5139
WoS: 000366585800001
Scopus: 2-s2.0-84957567719
Collections
Institution/Community
Hemijski fakultet / Faculty of ChemistryTY - JOUR AU - Opsenica, Dejan M. AU - Radivojević, Jelena AU - Matić, Ivana Z. AU - Štajner, Tijana AU - Knezevic-Usaj, Slavica AU - Đurković-Đaković, Olgica AU - Šolaja, Bogdan A. PY - 2015 UR - https://cherry.chem.bg.ac.rs/handle/123456789/2010 AB - New cyclohexylidene 1,2,4,5-tetraoxanes with polar guanidine and urea based groups were synthesized and evaluated for their antimalarial activity against chloroquine resistant and susceptible Plasmodium falciparum strains. The derivatives showed moderate, nM range antimalarial activities and low cytotoxicity. The N-phenylurea derivative 24 exhibited the best resistance indices (RIW2 = 0.44, RITM91C235 = 0.80) and was not toxic against human normal peripheral blood mononuclear cells (IC50 gt 200 mu M). Seven derivatives were tested in vitro against four human cancer cell lines and they demonstrated high selectivity toward leukaemia 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(-1) day(-1) for 8 days allowed the survival of 20 % of infected mice, thus demonstrating the high potential of tetraoxanes for the treatment of apicomplexan parasites. PB - Serbian Chemical Soc, Belgrade T2 - Journal of the Serbian Chemical Society T1 - Tetraoxanes as inhibitors of apicomplexan parasites Plasmodium falciparum and Toxoplasma gondii growth and anti-cancer molecules VL - 80 IS - 11 SP - 1339 DO - 10.2298/JSC150430063O ER -
@article{ author = "Opsenica, Dejan M. and Radivojević, Jelena and Matić, Ivana Z. and Štajner, Tijana and Knezevic-Usaj, Slavica and Đurković-Đaković, Olgica and Šolaja, Bogdan A.", year = "2015", abstract = "New cyclohexylidene 1,2,4,5-tetraoxanes with polar guanidine and urea based groups were synthesized and evaluated for their antimalarial activity against chloroquine resistant and susceptible Plasmodium falciparum strains. The derivatives showed moderate, nM range antimalarial activities and low cytotoxicity. The N-phenylurea derivative 24 exhibited the best resistance indices (RIW2 = 0.44, RITM91C235 = 0.80) and was not toxic against human normal peripheral blood mononuclear cells (IC50 gt 200 mu M). Seven derivatives were tested in vitro against four human cancer cell lines and they demonstrated high selectivity toward leukaemia 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(-1) day(-1) for 8 days allowed the survival of 20 % of infected mice, thus demonstrating the high potential of tetraoxanes for the treatment of apicomplexan parasites.", publisher = "Serbian Chemical Soc, Belgrade", journal = "Journal of the Serbian Chemical Society", title = "Tetraoxanes as inhibitors of apicomplexan parasites Plasmodium falciparum and Toxoplasma gondii growth and anti-cancer molecules", volume = "80", number = "11", pages = "1339", doi = "10.2298/JSC150430063O" }
Opsenica, D. M., Radivojević, J., Matić, I. Z., Štajner, T., Knezevic-Usaj, S., Đurković-Đaković, O.,& Šolaja, B. A.. (2015). Tetraoxanes as inhibitors of apicomplexan parasites Plasmodium falciparum and Toxoplasma gondii growth and anti-cancer molecules. in Journal of the Serbian Chemical Society Serbian Chemical Soc, Belgrade., 80(11), 1339. https://doi.org/10.2298/JSC150430063O
Opsenica DM, Radivojević J, Matić IZ, Štajner T, Knezevic-Usaj S, Đurković-Đaković O, Šolaja BA. Tetraoxanes as inhibitors of apicomplexan parasites Plasmodium falciparum and Toxoplasma gondii growth and anti-cancer molecules. in Journal of the Serbian Chemical Society. 2015;80(11):1339. doi:10.2298/JSC150430063O .
Opsenica, Dejan M., Radivojević, Jelena, Matić, Ivana Z., Štajner, Tijana, Knezevic-Usaj, Slavica, Đurković-Đaković, Olgica, Šolaja, Bogdan A., "Tetraoxanes as inhibitors of apicomplexan parasites Plasmodium falciparum and Toxoplasma gondii growth and anti-cancer molecules" in Journal of the Serbian Chemical Society, 80, no. 11 (2015):1339, https://doi.org/10.2298/JSC150430063O . .