TY  - JOUR
AU  - Opsenica, Igor
AU  - Terzić-Jovanović, Nataša
AU  - Opsenica, Dejan M.
AU  - Angelovski, Goran
AU  - Lehnig, Manfred
AU  - Eilbracht, Peter
AU  - Tinant, Bernard
AU  - Juranić, Zorica D.
AU  - Smith, Kirsten S.
AU  - Yang, Young S.
AU  - Diaz, Damaris S.
AU  - Smith, Philip L.
AU  - Milhous, Wilbur K.
AU  - Dokovic, Dejan
AU  - Šolaja, Bogdan A.
PY  - 2006
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/783
AB  - Mixed tetraoxanes 5a and 13 synthesized from cholic acid and 4-oxocyclohexanecarboxylic acid were as active as artemisinin against chloroquine-susceptible, chloroquine-resistant, and multidrug-resistant Plasmodium falciparum strains (IC50, IC90). Most active 13 is metabolically stable in in vitro metabolism studies. In vivo studies on tetraoxanes with a C(4'') methyl group afforded compound 15, which cured 4/5 mice at 600 and 200 mg, kg(-1), day(-1), and 2/5 mice at 50 mg, kg(-1), day(-1), showing no toxic effects. Tetraoxane 19 was an extremely active antiproliferative with LC50 of 17 nM and maximum tolerated dose of 400 mg/kg. In Fe(II)-induced scission of tetraoxane antimalarials only RO center dot radicals were detected by EPR experiments. This finding and the indication of Fe(IV)=O species led us to propose that RO center dot radicals are probably capable of inducing the parasite's death. Our results suggest that C radicals are possibly not the only lethal species derived from peroxide prodrug antimalarials, as currently believed.
PB  - Amer Chemical Soc, Washington
T2  - Journal of Medicinal Chemistry
T1  - Tetraoxane antimalarials and their reaction with Fe(II)
VL  - 49
IS  - 13
SP  - 3790
EP  - 3799
DO  - 10.1021/jm050966r
ER  - 

@article{
author = "Opsenica, Igor and Terzić-Jovanović, Nataša and Opsenica, Dejan M. and Angelovski, Goran and Lehnig, Manfred and Eilbracht, Peter and Tinant, Bernard and Juranić, Zorica D. and Smith, Kirsten S. and Yang, Young S. and Diaz, Damaris S. and Smith, Philip L. and Milhous, Wilbur K. and Dokovic, Dejan and Šolaja, Bogdan A.",
year = "2006",
abstract = "Mixed tetraoxanes 5a and 13 synthesized from cholic acid and 4-oxocyclohexanecarboxylic acid were as active as artemisinin against chloroquine-susceptible, chloroquine-resistant, and multidrug-resistant Plasmodium falciparum strains (IC50, IC90). Most active 13 is metabolically stable in in vitro metabolism studies. In vivo studies on tetraoxanes with a C(4'') methyl group afforded compound 15, which cured 4/5 mice at 600 and 200 mg, kg(-1), day(-1), and 2/5 mice at 50 mg, kg(-1), day(-1), showing no toxic effects. Tetraoxane 19 was an extremely active antiproliferative with LC50 of 17 nM and maximum tolerated dose of 400 mg/kg. In Fe(II)-induced scission of tetraoxane antimalarials only RO center dot radicals were detected by EPR experiments. This finding and the indication of Fe(IV)=O species led us to propose that RO center dot radicals are probably capable of inducing the parasite's death. Our results suggest that C radicals are possibly not the only lethal species derived from peroxide prodrug antimalarials, as currently believed.",
publisher = "Amer Chemical Soc, Washington",
journal = "Journal of Medicinal Chemistry",
title = "Tetraoxane antimalarials and their reaction with Fe(II)",
volume = "49",
number = "13",
pages = "3790-3799",
doi = "10.1021/jm050966r"
}

Opsenica, I., Terzić-Jovanović, N., Opsenica, D. M., Angelovski, G., Lehnig, M., Eilbracht, P., Tinant, B., Juranić, Z. D., Smith, K. S., Yang, Y. S., Diaz, D. S., Smith, P. L., Milhous, W. K., Dokovic, D.,& Šolaja, B. A.. (2006). Tetraoxane antimalarials and their reaction with Fe(II). in Journal of Medicinal Chemistry
Amer Chemical Soc, Washington., 49(13), 3790-3799.
https://doi.org/10.1021/jm050966r

Opsenica I, Terzić-Jovanović N, Opsenica DM, Angelovski G, Lehnig M, Eilbracht P, Tinant B, Juranić ZD, Smith KS, Yang YS, Diaz DS, Smith PL, Milhous WK, Dokovic D, Šolaja BA. Tetraoxane antimalarials and their reaction with Fe(II). in Journal of Medicinal Chemistry. 2006;49(13):3790-3799.
doi:10.1021/jm050966r .

Opsenica, Igor, Terzić-Jovanović, Nataša, Opsenica, Dejan M., Angelovski, Goran, Lehnig, Manfred, Eilbracht, Peter, Tinant, Bernard, Juranić, Zorica D., Smith, Kirsten S., Yang, Young S., Diaz, Damaris S., Smith, Philip L., Milhous, Wilbur K., Dokovic, Dejan, Šolaja, Bogdan A., "Tetraoxane antimalarials and their reaction with Fe(II)" in Journal of Medicinal Chemistry, 49, no. 13 (2006):3790-3799,
https://doi.org/10.1021/jm050966r . .