TY  - JOUR
AU  - Opsenica, Igor
AU  - Terzić-Jovanović, Nataša
AU  - Opsenica, Dejan
AU  - Angelovski, Goran
AU  - Lehnig, Manfred
AU  - Eilbracht, Peter
AU  - Tinant, Bernard
AU  - Juranić, Zorica
AU  - Smith, Kirsten S.
AU  - Yang, Young S.
AU  - Diaz, Damaris S.
AU  - Smith, Philip L.
AU  - Milhous, Wilbur K.
AU  - Đoković, Dejan
AU  - Šolaja, Bogdan
PY  - 2006
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/3096
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  - American Chemical Society (ACS)
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 and Angelovski, Goran and Lehnig, Manfred and Eilbracht, Peter and Tinant, Bernard and Juranić, Zorica and Smith, Kirsten S. and Yang, Young S. and Diaz, Damaris S. and Smith, Philip L. and Milhous, Wilbur K. and Đoković, Dejan and Šolaja, Bogdan",
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 = "American Chemical Society (ACS)",
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., Angelovski, G., Lehnig, M., Eilbracht, P., Tinant, B., Juranić, Z., Smith, K. S., Yang, Y. S., Diaz, D. S., Smith, P. L., Milhous, W. K., Đoković, D.,& Šolaja, B.. (2006). Tetraoxane antimalarials and their reaction with Fe(II). in Journal of Medicinal Chemistry
American Chemical Society (ACS)., 49(13), 3790-3799.
https://doi.org/10.1021/jm050966r

Opsenica I, Terzić-Jovanović N, Opsenica D, Angelovski G, Lehnig M, Eilbracht P, Tinant B, Juranić Z, Smith KS, Yang YS, Diaz DS, Smith PL, Milhous WK, Đoković D, Šolaja B. 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, Angelovski, Goran, Lehnig, Manfred, Eilbracht, Peter, Tinant, Bernard, Juranić, Zorica, Smith, Kirsten S., Yang, Young S., Diaz, Damaris S., Smith, Philip L., Milhous, Wilbur K., Đoković, Dejan, Šolaja, Bogdan, "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 . .

TY  - JOUR
AU  - Opsenica, Dejan
AU  - Angelovski, Goran
AU  - Pocsfalvi, Gabriella
AU  - Juranić, Zorica
AU  - Žižak, Željko
AU  - Kyle, Dennis
AU  - Milhous, Wilbur K.
AU  - Šolaja, Bogdan
PY  - 2003
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/7446
AB  - Several cis and trans bis-steroidal 1,2,4,5-tetraoxanes possessing amide terminus were synthesised and evaluated as antimalarials and antiproliferatives. The compounds exhibited submicromolar antimalarial activity against Plasmodium falciparum D6 and W2 strains. The existence of HN-C(O) moiety was found necessary for pronounced antimalarial and antiproliferative activity. In antiproliferative screen, the trans tetraoxane 6 was found to exhibit a pronounced cytotoxicity on 14 cancer cell lines. In addition, tetraoxanes 11 and 12 exhibited significant cytotoxic activity too; microscopic examination of treated HeLa cells showed morphological appearance reminiscent for apoptosis (condensed and/or fragmented nuclei).
PB  - Elsevier
T2  - Bioorganic and Medicinal Chemistry
T1  - Antimalarial and antiproliferative evaluation of bis-steroidal tetraoxanes
VL  - 11
IS  - 13
SP  - 2761
EP  - 2768
DO  - 10.1016/S0968-0896(03)00224-4
ER  - 

@article{
author = "Opsenica, Dejan and Angelovski, Goran and Pocsfalvi, Gabriella and Juranić, Zorica and Žižak, Željko and Kyle, Dennis and Milhous, Wilbur K. and Šolaja, Bogdan",
year = "2003",
abstract = "Several cis and trans bis-steroidal 1,2,4,5-tetraoxanes possessing amide terminus were synthesised and evaluated as antimalarials and antiproliferatives. The compounds exhibited submicromolar antimalarial activity against Plasmodium falciparum D6 and W2 strains. The existence of HN-C(O) moiety was found necessary for pronounced antimalarial and antiproliferative activity. In antiproliferative screen, the trans tetraoxane 6 was found to exhibit a pronounced cytotoxicity on 14 cancer cell lines. In addition, tetraoxanes 11 and 12 exhibited significant cytotoxic activity too; microscopic examination of treated HeLa cells showed morphological appearance reminiscent for apoptosis (condensed and/or fragmented nuclei).",
publisher = "Elsevier",
journal = "Bioorganic and Medicinal Chemistry",
title = "Antimalarial and antiproliferative evaluation of bis-steroidal tetraoxanes",
volume = "11",
number = "13",
pages = "2761-2768",
doi = "10.1016/S0968-0896(03)00224-4"
}

Opsenica, D., Angelovski, G., Pocsfalvi, G., Juranić, Z., Žižak, Ž., Kyle, D., Milhous, W. K.,& Šolaja, B.. (2003). Antimalarial and antiproliferative evaluation of bis-steroidal tetraoxanes. in Bioorganic and Medicinal Chemistry
Elsevier., 11(13), 2761-2768.
https://doi.org/10.1016/S0968-0896(03)00224-4

Opsenica D, Angelovski G, Pocsfalvi G, Juranić Z, Žižak Ž, Kyle D, Milhous WK, Šolaja B. Antimalarial and antiproliferative evaluation of bis-steroidal tetraoxanes. in Bioorganic and Medicinal Chemistry. 2003;11(13):2761-2768.
doi:10.1016/S0968-0896(03)00224-4 .

Opsenica, Dejan, Angelovski, Goran, Pocsfalvi, Gabriella, Juranić, Zorica, Žižak, Željko, Kyle, Dennis, Milhous, Wilbur K., Šolaja, Bogdan, "Antimalarial and antiproliferative evaluation of bis-steroidal tetraoxanes" in Bioorganic and Medicinal Chemistry, 11, no. 13 (2003):2761-2768,
https://doi.org/10.1016/S0968-0896(03)00224-4 . .