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

2015
Authors
Opsenica, Dejan
Radivojevic, Jelena
Matić, Ivana Z.

Štajner, Tijana

Knezevic-Usaj, Slavica

Djurkovic-Djakovic, Olgica

Šolaja, Bogdan

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 > 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
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