TY  - JOUR
AU  - Opsenica, Dejan M.
AU  - Terzić-Jovanović, Nataša
AU  - Smith, Philip L.
AU  - Yang, Youngsun
AU  - Anova, Lalaine
AU  - Smith, Kirsten S.
AU  - Šolaja, Bogdan A.
PY  - 2008
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/957
AB  - Eleven new tetraoxanes possessing cholic acid-derived carrier and isopropylidene moiety were synthesized and were tested in vitro and in vivo. In vitro screening revealed that nine of them were more potent against CQ-resistant W2 than CQ-susceptible D6 strain and that two of them were equally or more potent than artemisinin and mefloquine against multi- drug resistant TM91C235 strain. Amine 8 cured all mice at the dose of 160 mg/kg/day, while the anilide 9 exhibited MCD  lt = 20 mg/kg/day. The diol 13 was most potent antiproliferative with GI(50), TGI, LC50 MG_MID 0.98 mu M, 3.80 mu M, 11.22 mu M, respectively. All tested compounds showed no toxic effects. (c) 2008 Elsevier Ltd. All rights reserved.
PB  - Pergamon-Elsevier Science Ltd, Oxford
T2  - Bioorganic and Medicinal Chemistry
T1  - Mixed tetraoxanes containing the acetone subunit as antimalarials
VL  - 16
IS  - 14
SP  - 7039
EP  - 7045
DO  - 10.1016/j.bmc.2008.05.017
ER  - 

@article{
author = "Opsenica, Dejan M. and Terzić-Jovanović, Nataša and Smith, Philip L. and Yang, Youngsun and Anova, Lalaine and Smith, Kirsten S. and Šolaja, Bogdan A.",
year = "2008",
abstract = "Eleven new tetraoxanes possessing cholic acid-derived carrier and isopropylidene moiety were synthesized and were tested in vitro and in vivo. In vitro screening revealed that nine of them were more potent against CQ-resistant W2 than CQ-susceptible D6 strain and that two of them were equally or more potent than artemisinin and mefloquine against multi- drug resistant TM91C235 strain. Amine 8 cured all mice at the dose of 160 mg/kg/day, while the anilide 9 exhibited MCD  lt = 20 mg/kg/day. The diol 13 was most potent antiproliferative with GI(50), TGI, LC50 MG_MID 0.98 mu M, 3.80 mu M, 11.22 mu M, respectively. All tested compounds showed no toxic effects. (c) 2008 Elsevier Ltd. All rights reserved.",
publisher = "Pergamon-Elsevier Science Ltd, Oxford",
journal = "Bioorganic and Medicinal Chemistry",
title = "Mixed tetraoxanes containing the acetone subunit as antimalarials",
volume = "16",
number = "14",
pages = "7039-7045",
doi = "10.1016/j.bmc.2008.05.017"
}

Opsenica, D. M., Terzić-Jovanović, N., Smith, P. L., Yang, Y., Anova, L., Smith, K. S.,& Šolaja, B. A.. (2008). Mixed tetraoxanes containing the acetone subunit as antimalarials. in Bioorganic and Medicinal Chemistry
Pergamon-Elsevier Science Ltd, Oxford., 16(14), 7039-7045.
https://doi.org/10.1016/j.bmc.2008.05.017

Opsenica DM, Terzić-Jovanović N, Smith PL, Yang Y, Anova L, Smith KS, Šolaja BA. Mixed tetraoxanes containing the acetone subunit as antimalarials. in Bioorganic and Medicinal Chemistry. 2008;16(14):7039-7045.
doi:10.1016/j.bmc.2008.05.017 .

Opsenica, Dejan M., Terzić-Jovanović, Nataša, Smith, Philip L., Yang, Youngsun, Anova, Lalaine, Smith, Kirsten S., Šolaja, Bogdan A., "Mixed tetraoxanes containing the acetone subunit as antimalarials" in Bioorganic and Medicinal Chemistry, 16, no. 14 (2008):7039-7045,
https://doi.org/10.1016/j.bmc.2008.05.017 . .

TY  - JOUR
AU  - Šolaja, Bogdan A.
AU  - Opsenica, Dejan M.
AU  - Smith, Kirsten S.
AU  - Milhous, Wilbur K.
AU  - Terzić-Jovanović, Nataša
AU  - Opsenica, Igor
AU  - Burnett, James C.
AU  - Nuss, Jon
AU  - Gussio, Rick
AU  - Bavari, Sina
PY  - 2008
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/961
AB  - We report on the initial result of the coupling of 4-amino7-chloroquinoline with steroidal and adamantane constituents to provide small molecules with excellent in vitro antimalarial activities (IC90 (W2) down to 6.74 nM). The same entities also inhibit the botulinum neurotoxin serotype A light chain metalloprotease at low nlicromolar levels (7-3 1 yM). Interestingly. structural features imparting increased antimalarial activity also provide increased inetalloprotease inhibition, thus allowing for simultaneous compound optimizations against distinct targets.
PB  - Amer Chemical Soc, Washington
T2  - Journal of Medicinal Chemistry
T1  - Novel 4-aminoquinolines active against chloroquine-resistant and sensitive P. falciparum strains that also inhibit botulinum serotype A
VL  - 51
IS  - 15
SP  - 4388
EP  - 4391
DO  - 10.1021/jm800737y
ER  - 

@article{
author = "Šolaja, Bogdan A. and Opsenica, Dejan M. and Smith, Kirsten S. and Milhous, Wilbur K. and Terzić-Jovanović, Nataša and Opsenica, Igor and Burnett, James C. and Nuss, Jon and Gussio, Rick and Bavari, Sina",
year = "2008",
abstract = "We report on the initial result of the coupling of 4-amino7-chloroquinoline with steroidal and adamantane constituents to provide small molecules with excellent in vitro antimalarial activities (IC90 (W2) down to 6.74 nM). The same entities also inhibit the botulinum neurotoxin serotype A light chain metalloprotease at low nlicromolar levels (7-3 1 yM). Interestingly. structural features imparting increased antimalarial activity also provide increased inetalloprotease inhibition, thus allowing for simultaneous compound optimizations against distinct targets.",
publisher = "Amer Chemical Soc, Washington",
journal = "Journal of Medicinal Chemistry",
title = "Novel 4-aminoquinolines active against chloroquine-resistant and sensitive P. falciparum strains that also inhibit botulinum serotype A",
volume = "51",
number = "15",
pages = "4388-4391",
doi = "10.1021/jm800737y"
}

Šolaja, B. A., Opsenica, D. M., Smith, K. S., Milhous, W. K., Terzić-Jovanović, N., Opsenica, I., Burnett, J. C., Nuss, J., Gussio, R.,& Bavari, S.. (2008). Novel 4-aminoquinolines active against chloroquine-resistant and sensitive P. falciparum strains that also inhibit botulinum serotype A. in Journal of Medicinal Chemistry
Amer Chemical Soc, Washington., 51(15), 4388-4391.
https://doi.org/10.1021/jm800737y

Šolaja BA, Opsenica DM, Smith KS, Milhous WK, Terzić-Jovanović N, Opsenica I, Burnett JC, Nuss J, Gussio R, Bavari S. Novel 4-aminoquinolines active against chloroquine-resistant and sensitive P. falciparum strains that also inhibit botulinum serotype A. in Journal of Medicinal Chemistry. 2008;51(15):4388-4391.
doi:10.1021/jm800737y .

Šolaja, Bogdan A., Opsenica, Dejan M., Smith, Kirsten S., Milhous, Wilbur K., Terzić-Jovanović, Nataša, Opsenica, Igor, Burnett, James C., Nuss, Jon, Gussio, Rick, Bavari, Sina, "Novel 4-aminoquinolines active against chloroquine-resistant and sensitive P. falciparum strains that also inhibit botulinum serotype A" in Journal of Medicinal Chemistry, 51, no. 15 (2008):4388-4391,
https://doi.org/10.1021/jm800737y . .

TY  - JOUR
AU  - Opsenica, Igor
AU  - Opsenica, Dejan M.
AU  - Lanteri, Charlotte Anne
AU  - Anova, Lalaine
AU  - Milhous, Wilbur K.
AU  - Smith, Kirsten S.
AU  - Šolaja, Bogdan A.
PY  - 2008
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/975
AB  - The synthesis of the chimeric molecules consisting of two pharmacophores, tetraoxane and 7-chloro-4-aminoquinoline, is reported. The tetraoxanes 2, 4, and 8 show relatively potent in vitro antimalarial activities, with IC90 values for the Plasmodium falciparum strain W2 of 2.26, 12.44, and 10.74 nM, respectively. In addition, two compounds, 2 and 4, cured mice in a modified Thompson test for antimalarial blood stage activity, with a minimum curative dose of 80 mg/kg, a minimum active dose of 20 mg/kg/day, and a maximum tolerated dose of  gt  960 mg/kg.
PB  - Amer Chemical Soc, Washington
T2  - Journal of Medicinal Chemistry
T1  - New chimeric antimalarials with 4-aminoquinoline moiety linked to a tetraoxane skeleton
VL  - 51
IS  - 19
SP  - 6216
EP  - 6219
DO  - 10.1021/jm8006905
ER  - 

@article{
author = "Opsenica, Igor and Opsenica, Dejan M. and Lanteri, Charlotte Anne and Anova, Lalaine and Milhous, Wilbur K. and Smith, Kirsten S. and Šolaja, Bogdan A.",
year = "2008",
abstract = "The synthesis of the chimeric molecules consisting of two pharmacophores, tetraoxane and 7-chloro-4-aminoquinoline, is reported. The tetraoxanes 2, 4, and 8 show relatively potent in vitro antimalarial activities, with IC90 values for the Plasmodium falciparum strain W2 of 2.26, 12.44, and 10.74 nM, respectively. In addition, two compounds, 2 and 4, cured mice in a modified Thompson test for antimalarial blood stage activity, with a minimum curative dose of 80 mg/kg, a minimum active dose of 20 mg/kg/day, and a maximum tolerated dose of  gt  960 mg/kg.",
publisher = "Amer Chemical Soc, Washington",
journal = "Journal of Medicinal Chemistry",
title = "New chimeric antimalarials with 4-aminoquinoline moiety linked to a tetraoxane skeleton",
volume = "51",
number = "19",
pages = "6216-6219",
doi = "10.1021/jm8006905"
}

Opsenica, I., Opsenica, D. M., Lanteri, C. A., Anova, L., Milhous, W. K., Smith, K. S.,& Šolaja, B. A.. (2008). New chimeric antimalarials with 4-aminoquinoline moiety linked to a tetraoxane skeleton. in Journal of Medicinal Chemistry
Amer Chemical Soc, Washington., 51(19), 6216-6219.
https://doi.org/10.1021/jm8006905

Opsenica I, Opsenica DM, Lanteri CA, Anova L, Milhous WK, Smith KS, Šolaja BA. New chimeric antimalarials with 4-aminoquinoline moiety linked to a tetraoxane skeleton. in Journal of Medicinal Chemistry. 2008;51(19):6216-6219.
doi:10.1021/jm8006905 .

Opsenica, Igor, Opsenica, Dejan M., Lanteri, Charlotte Anne, Anova, Lalaine, Milhous, Wilbur K., Smith, Kirsten S., Šolaja, Bogdan A., "New chimeric antimalarials with 4-aminoquinoline moiety linked to a tetraoxane skeleton" in Journal of Medicinal Chemistry, 51, no. 19 (2008):6216-6219,
https://doi.org/10.1021/jm8006905 . .

TY  - JOUR
AU  - Opsenica, Igor
AU  - Opsenica, Dejan M.
AU  - Smith, Kirsten S.
AU  - Milhous, Wilbur K.
AU  - Šolaja, Bogdan A.
PY  - 2008
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/926
AB  - The development of widespread drug resistance to chloroquine (CQ(a)) has resulted in severe health issues for countries in malaria endemic regions. The antimalarial properties of artemisinin 2 and of other peroxides, such as 1,2,4,5-tetraoxacy-cloalkanes (tetraoxanes), have recently begun to be exploited in the development of new approaches to fighting CQ-resistant strains of malaria. New tetraoxanes employing a steroidal backbone have now been prepared that are highly active, are inexpensive, and demonstrate low toXieity.(5,6) A part of our research in this field is focused on the development of a new type of tetraoxane with nonidentical substituents(6) that utilize a steroid and small cyclohexylidene carriers possessing secondary amide bonds. Also, during our work in this field we discovered that tetraoxanes are unusually stable, even. at pH 1.6,(6c) a characteristic that subsequently allowed the synthesis of many interesting derivatives. This communication encompasses the synthesis of various amino-functionalized antimalarials based on the appreciable stability of the tetraoxane moiety to reaction conditions such as reductive amination and LiAlH4 reduction. Their respective antimalarial activities and the pronounced antiproliferative activity of certain products are reported along with in vitro metabolism studies.
PB  - Amer Chemical Soc, Washington
T2  - Journal of Medicinal Chemistry
T1  - Chemical stability of the peroxide bond enables diversified synthesis of potent tetraoxane Antimalarials
VL  - 51
IS  - 7
SP  - 2261
EP  - 2266
DO  - 10.1021/jm701417a
ER  - 

@article{
author = "Opsenica, Igor and Opsenica, Dejan M. and Smith, Kirsten S. and Milhous, Wilbur K. and Šolaja, Bogdan A.",
year = "2008",
abstract = "The development of widespread drug resistance to chloroquine (CQ(a)) has resulted in severe health issues for countries in malaria endemic regions. The antimalarial properties of artemisinin 2 and of other peroxides, such as 1,2,4,5-tetraoxacy-cloalkanes (tetraoxanes), have recently begun to be exploited in the development of new approaches to fighting CQ-resistant strains of malaria. New tetraoxanes employing a steroidal backbone have now been prepared that are highly active, are inexpensive, and demonstrate low toXieity.(5,6) A part of our research in this field is focused on the development of a new type of tetraoxane with nonidentical substituents(6) that utilize a steroid and small cyclohexylidene carriers possessing secondary amide bonds. Also, during our work in this field we discovered that tetraoxanes are unusually stable, even. at pH 1.6,(6c) a characteristic that subsequently allowed the synthesis of many interesting derivatives. This communication encompasses the synthesis of various amino-functionalized antimalarials based on the appreciable stability of the tetraoxane moiety to reaction conditions such as reductive amination and LiAlH4 reduction. Their respective antimalarial activities and the pronounced antiproliferative activity of certain products are reported along with in vitro metabolism studies.",
publisher = "Amer Chemical Soc, Washington",
journal = "Journal of Medicinal Chemistry",
title = "Chemical stability of the peroxide bond enables diversified synthesis of potent tetraoxane Antimalarials",
volume = "51",
number = "7",
pages = "2261-2266",
doi = "10.1021/jm701417a"
}

Opsenica, I., Opsenica, D. M., Smith, K. S., Milhous, W. K.,& Šolaja, B. A.. (2008). Chemical stability of the peroxide bond enables diversified synthesis of potent tetraoxane Antimalarials. in Journal of Medicinal Chemistry
Amer Chemical Soc, Washington., 51(7), 2261-2266.
https://doi.org/10.1021/jm701417a

Opsenica I, Opsenica DM, Smith KS, Milhous WK, Šolaja BA. Chemical stability of the peroxide bond enables diversified synthesis of potent tetraoxane Antimalarials. in Journal of Medicinal Chemistry. 2008;51(7):2261-2266.
doi:10.1021/jm701417a .

Opsenica, Igor, Opsenica, Dejan M., Smith, Kirsten S., Milhous, Wilbur K., Šolaja, Bogdan A., "Chemical stability of the peroxide bond enables diversified synthesis of potent tetraoxane Antimalarials" in Journal of Medicinal Chemistry, 51, no. 7 (2008):2261-2266,
https://doi.org/10.1021/jm701417a . .

TY  - JOUR
AU  - Terzić-Jovanović, Nataša
AU  - Opsenica, Dejan M.
AU  - Milić, Dragana
AU  - Tinant, Bernard
AU  - Smith, Kirsten S.
AU  - Milhous, Wilbur K.
AU  - Šolaja, Bogdan A.
PY  - 2007
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/882
AB  - The synthesis of deoxycholic acid (DCA)- and cholic acid (CA)-derived mixed tetraoxanes revealed that N-(2-dimethylamino)ethyl derivatives are potent antimalarials in vitro and in vivo. The tetraoxanes presented in this paper are dual inhibitors: besides curing mice in vivo without observed toxic effects, they kill cancer cell lines at very low concentrations. For example, DCA and CA derivatives 16 and 25 cured 3/5 (160 mg/kg/day) and 2/5 (40 mg/kg/day, MTD  gt 960 mg/kg), respectively, and they were extremely active against melanoma LOX IMVI cancer, LC50 = 22 nM and 69 nM, respectively.
PB  - Amer Chemical Soc, Washington
T2  - Journal of Medicinal Chemistry
T1  - Deoxycholic acid-derived tetraoxane antimalarials and antiproliferatives
VL  - 50
IS  - 21
SP  - 5118
EP  - 5127
DO  - 10.1021/jm070684m
ER  - 

@article{
author = "Terzić-Jovanović, Nataša and Opsenica, Dejan M. and Milić, Dragana and Tinant, Bernard and Smith, Kirsten S. and Milhous, Wilbur K. and Šolaja, Bogdan A.",
year = "2007",
abstract = "The synthesis of deoxycholic acid (DCA)- and cholic acid (CA)-derived mixed tetraoxanes revealed that N-(2-dimethylamino)ethyl derivatives are potent antimalarials in vitro and in vivo. The tetraoxanes presented in this paper are dual inhibitors: besides curing mice in vivo without observed toxic effects, they kill cancer cell lines at very low concentrations. For example, DCA and CA derivatives 16 and 25 cured 3/5 (160 mg/kg/day) and 2/5 (40 mg/kg/day, MTD  gt 960 mg/kg), respectively, and they were extremely active against melanoma LOX IMVI cancer, LC50 = 22 nM and 69 nM, respectively.",
publisher = "Amer Chemical Soc, Washington",
journal = "Journal of Medicinal Chemistry",
title = "Deoxycholic acid-derived tetraoxane antimalarials and antiproliferatives",
volume = "50",
number = "21",
pages = "5118-5127",
doi = "10.1021/jm070684m"
}

Terzić-Jovanović, N., Opsenica, D. M., Milić, D., Tinant, B., Smith, K. S., Milhous, W. K.,& Šolaja, B. A.. (2007). Deoxycholic acid-derived tetraoxane antimalarials and antiproliferatives. in Journal of Medicinal Chemistry
Amer Chemical Soc, Washington., 50(21), 5118-5127.
https://doi.org/10.1021/jm070684m

Terzić-Jovanović N, Opsenica DM, Milić D, Tinant B, Smith KS, Milhous WK, Šolaja BA. Deoxycholic acid-derived tetraoxane antimalarials and antiproliferatives. in Journal of Medicinal Chemistry. 2007;50(21):5118-5127.
doi:10.1021/jm070684m .

Terzić-Jovanović, Nataša, Opsenica, Dejan M., Milić, Dragana, Tinant, Bernard, Smith, Kirsten S., Milhous, Wilbur K., Šolaja, Bogdan A., "Deoxycholic acid-derived tetraoxane antimalarials and antiproliferatives" in Journal of Medicinal Chemistry, 50, no. 21 (2007):5118-5127,
https://doi.org/10.1021/jm070684m . .

TY  - JOUR
AU  - Opsenica, Igor
AU  - Opsenica, Dejan M.
AU  - Jadranin, Milka
AU  - Smith, Kirsten S.
AU  - Milhous, Wilbur K.
AU  - Stratakis, Manolis
AU  - Šolaja, Bogdan A.
PY  - 2007
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/901
AB  - Several dicyclohexylidene tetraoxanes were prepared in order to gain a further insight into structure-activity relationship of this kind of antimalarials. The tetraoxanes 2-5, obtained as a cis/trans mixture, showed pronounced antimalarial activity against Plasmodium falciparum chloroquine susceptible D6, chloroquine resistant W2 and multidrug-resistant TM91C235 (Thailand) strains. They have better than or similar activity to the corresponding desmethyl dicyclohexylidene derivatives. Two chimeric endoperoxides with superior antimalarial activity to the natural product ascaridole were also synthesized.
AB  - U ovom radu prikazana je sinteza nekoliko dicikiloheksilidenskih tetraoksana u cilju sagledavanja odnosa struktura-aktivnost ove vrste antimalarika. Jedinjenja 2-5 dobijena kao (cis,trans)-smese pokazala su izraženu antimalarijsku aktivnost prema D6, W2 i TM91C235 (Thailand) sojevima P. falciparum. Ona imaju bolju ili sličnu aktivnost od odgovarajućih desmetil cikloheksilidenskih derivata. Sintetisana su i dva endoperoksida himerne strukture znatno izraženije aktivnosti od prirodnog proizvoda askaridola. .
PB  - Serbian Chemical Soc, Belgrade
T2  - Journal of the Serbian Chemical Society
T1  - On peroxide antimalarials
T1  - O peroksidnim antimalaricima
VL  - 72
IS  - 12
SP  - 1181
EP  - 1190
DO  - 10.2298/JSC0712181O
ER  - 

@article{
author = "Opsenica, Igor and Opsenica, Dejan M. and Jadranin, Milka and Smith, Kirsten S. and Milhous, Wilbur K. and Stratakis, Manolis and Šolaja, Bogdan A.",
year = "2007",
abstract = "Several dicyclohexylidene tetraoxanes were prepared in order to gain a further insight into structure-activity relationship of this kind of antimalarials. The tetraoxanes 2-5, obtained as a cis/trans mixture, showed pronounced antimalarial activity against Plasmodium falciparum chloroquine susceptible D6, chloroquine resistant W2 and multidrug-resistant TM91C235 (Thailand) strains. They have better than or similar activity to the corresponding desmethyl dicyclohexylidene derivatives. Two chimeric endoperoxides with superior antimalarial activity to the natural product ascaridole were also synthesized., U ovom radu prikazana je sinteza nekoliko dicikiloheksilidenskih tetraoksana u cilju sagledavanja odnosa struktura-aktivnost ove vrste antimalarika. Jedinjenja 2-5 dobijena kao (cis,trans)-smese pokazala su izraženu antimalarijsku aktivnost prema D6, W2 i TM91C235 (Thailand) sojevima P. falciparum. Ona imaju bolju ili sličnu aktivnost od odgovarajućih desmetil cikloheksilidenskih derivata. Sintetisana su i dva endoperoksida himerne strukture znatno izraženije aktivnosti od prirodnog proizvoda askaridola. .",
publisher = "Serbian Chemical Soc, Belgrade",
journal = "Journal of the Serbian Chemical Society",
title = "On peroxide antimalarials, O peroksidnim antimalaricima",
volume = "72",
number = "12",
pages = "1181-1190",
doi = "10.2298/JSC0712181O"
}

Opsenica, I., Opsenica, D. M., Jadranin, M., Smith, K. S., Milhous, W. K., Stratakis, M.,& Šolaja, B. A.. (2007). On peroxide antimalarials. in Journal of the Serbian Chemical Society
Serbian Chemical Soc, Belgrade., 72(12), 1181-1190.
https://doi.org/10.2298/JSC0712181O

Opsenica I, Opsenica DM, Jadranin M, Smith KS, Milhous WK, Stratakis M, Šolaja BA. On peroxide antimalarials. in Journal of the Serbian Chemical Society. 2007;72(12):1181-1190.
doi:10.2298/JSC0712181O .

Opsenica, Igor, Opsenica, Dejan M., Jadranin, Milka, Smith, Kirsten S., Milhous, Wilbur K., Stratakis, Manolis, Šolaja, Bogdan A., "On peroxide antimalarials" in Journal of the Serbian Chemical Society, 72, no. 12 (2007):1181-1190,
https://doi.org/10.2298/JSC0712181O . .

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 . .