TY  - JOUR
AU  - Cvijetić, Ilija
AU  - Žižak, Željko
AU  - Stanojković, Tatjana
AU  - Juranić, Zorica
AU  - Terzić-Jovanović, Nataša
AU  - Opsenica, Igor
AU  - Opsenica, Dejan
AU  - Juranić, Ivan
AU  - Drakulić, Branko
PY  - 2010
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/716
AB  - An alignment-free 3D QSAR study on antiproliferative activity of the thirty-three 1,2,4,5-tetraoxane derivatives toward two human dedifferentiated cell lines was reported. GRIND methodology, where descriptors are derived from GRID molecular interaction fields (MIF), were used It was found that pharmacophoric pattern attributed to the most potent derivatives Include amido NH of the primary or secondary amide, and the acetoxy fragments at positions 7 and 12 of steroid core which are, along with the tetraoxane ring, common for all studied compounds. Independently, simple multiple regression model obtained by using the whole-molecular properties, confirmed that the hydrophobicity and the H-bond donor properties are the main parameters influencing potency of compounds toward human cervix carcinoma (HeLa) and human malignant melanoma (FemX) cell lines Corollary, similar structural motifs are found to be Important for the potency toward both examined cell lines.
PB  - Elsevier France-Editions Scientifiques Medicales Elsevier, Paris
T2  - European Journal of Medicinal Chemistry
T1  - An alignment independent 3D QSAR study of the antiproliferative activity of 1,2,4,5-tetraoxanes
VL  - 45
IS  - 10
SP  - 4570
EP  - 4577
DO  - 10.1016/j.ejmech.2010.07.019
ER  - 

@article{
author = "Cvijetić, Ilija and Žižak, Željko and Stanojković, Tatjana and Juranić, Zorica and Terzić-Jovanović, Nataša and Opsenica, Igor and Opsenica, Dejan and Juranić, Ivan and Drakulić, Branko",
year = "2010",
abstract = "An alignment-free 3D QSAR study on antiproliferative activity of the thirty-three 1,2,4,5-tetraoxane derivatives toward two human dedifferentiated cell lines was reported. GRIND methodology, where descriptors are derived from GRID molecular interaction fields (MIF), were used It was found that pharmacophoric pattern attributed to the most potent derivatives Include amido NH of the primary or secondary amide, and the acetoxy fragments at positions 7 and 12 of steroid core which are, along with the tetraoxane ring, common for all studied compounds. Independently, simple multiple regression model obtained by using the whole-molecular properties, confirmed that the hydrophobicity and the H-bond donor properties are the main parameters influencing potency of compounds toward human cervix carcinoma (HeLa) and human malignant melanoma (FemX) cell lines Corollary, similar structural motifs are found to be Important for the potency toward both examined cell lines.",
publisher = "Elsevier France-Editions Scientifiques Medicales Elsevier, Paris",
journal = "European Journal of Medicinal Chemistry",
title = "An alignment independent 3D QSAR study of the antiproliferative activity of 1,2,4,5-tetraoxanes",
volume = "45",
number = "10",
pages = "4570-4577",
doi = "10.1016/j.ejmech.2010.07.019"
}

Cvijetić, I., Žižak, Ž., Stanojković, T., Juranić, Z., Terzić-Jovanović, N., Opsenica, I., Opsenica, D., Juranić, I.,& Drakulić, B.. (2010). An alignment independent 3D QSAR study of the antiproliferative activity of 1,2,4,5-tetraoxanes. in European Journal of Medicinal Chemistry
Elsevier France-Editions Scientifiques Medicales Elsevier, Paris., 45(10), 4570-4577.
https://doi.org/10.1016/j.ejmech.2010.07.019

Cvijetić I, Žižak Ž, Stanojković T, Juranić Z, Terzić-Jovanović N, Opsenica I, Opsenica D, Juranić I, Drakulić B. An alignment independent 3D QSAR study of the antiproliferative activity of 1,2,4,5-tetraoxanes. in European Journal of Medicinal Chemistry. 2010;45(10):4570-4577.
doi:10.1016/j.ejmech.2010.07.019 .

Cvijetić, Ilija, Žižak, Željko, Stanojković, Tatjana, Juranić, Zorica, Terzić-Jovanović, Nataša, Opsenica, Igor, Opsenica, Dejan, Juranić, Ivan, Drakulić, Branko, "An alignment independent 3D QSAR study of the antiproliferative activity of 1,2,4,5-tetraoxanes" in European Journal of Medicinal Chemistry, 45, no. 10 (2010):4570-4577,
https://doi.org/10.1016/j.ejmech.2010.07.019 . .

TY  - JOUR
AU  - Žižak, Željko
AU  - Juranić, Zorica
AU  - Opsenica, Dejan
AU  - Šolaja, Bogdan
PY  - 2009
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/624
AB  - In this study we investigated the antiproliferative activity of six mixed steroidal tetraoxanes against various tumor cell lines, the toxicity against normal peripheral blood mononuclear cells (PBMC), and the mode of HeLa cell death induced by these compounds. Investigated tetraoxanes exerted a dose dependent antiproliferative action at micromolar concentrations toward target tumor cell lines. Treatment of HeLa cells for 24 h with all tetraoxanes induced apoptosis, as confirmed by morphological analysis and by the appearance of a typical ladder pattern in the DNA fragmentation assay.
T2  - Investigational New Drugs
T1  - Mixed steroidal tetraoxanes induce apoptotic cell death in tumor cells
VL  - 27
IS  - 5
SP  - 432
EP  - 439
DO  - 10.1007/s10637-008-9197-1
ER  - 

@article{
author = "Žižak, Željko and Juranić, Zorica and Opsenica, Dejan and Šolaja, Bogdan",
year = "2009",
abstract = "In this study we investigated the antiproliferative activity of six mixed steroidal tetraoxanes against various tumor cell lines, the toxicity against normal peripheral blood mononuclear cells (PBMC), and the mode of HeLa cell death induced by these compounds. Investigated tetraoxanes exerted a dose dependent antiproliferative action at micromolar concentrations toward target tumor cell lines. Treatment of HeLa cells for 24 h with all tetraoxanes induced apoptosis, as confirmed by morphological analysis and by the appearance of a typical ladder pattern in the DNA fragmentation assay.",
journal = "Investigational New Drugs",
title = "Mixed steroidal tetraoxanes induce apoptotic cell death in tumor cells",
volume = "27",
number = "5",
pages = "432-439",
doi = "10.1007/s10637-008-9197-1"
}

Žižak, Ž., Juranić, Z., Opsenica, D.,& Šolaja, B.. (2009). Mixed steroidal tetraoxanes induce apoptotic cell death in tumor cells. in Investigational New Drugs, 27(5), 432-439.
https://doi.org/10.1007/s10637-008-9197-1

Žižak Ž, Juranić Z, Opsenica D, Šolaja B. Mixed steroidal tetraoxanes induce apoptotic cell death in tumor cells. in Investigational New Drugs. 2009;27(5):432-439.
doi:10.1007/s10637-008-9197-1 .

Žižak, Željko, Juranić, Zorica, Opsenica, Dejan, Šolaja, Bogdan, "Mixed steroidal tetraoxanes induce apoptotic cell death in tumor cells" in Investigational New Drugs, 27, no. 5 (2009):432-439,
https://doi.org/10.1007/s10637-008-9197-1 . .

TY  - JOUR
AU  - Šegan, Sandra
AU  - Opsenica, Dejan
AU  - Šolaja, Bogdan
AU  - Milojković-Opsenica, Dušanka
PY  - 2009
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/579
AB  - Seven pairs of cis-trans isomers of bis-steroidal tetraoxanes have been examined by both normal-phase (NP) and reversed-phase (RP) planar chromatography. Unmodified silica gel was used with ethyl acetate-toluene and ethyl acetate-petroleum ether as mobile phases in typical normal-phase systems. CN-silica with the mobile phases methanol-water and acetone-water and RP-18 silica with water-organic modifier (methanol, acetone, or dioxane) mobile phases were used as reversed-phase systems. For the RP systems a good linear correlation was established between R M values and amount ([%] ν/ν ) of organic modifier in the mobile phase (usually r > 0.99). It was found that under both NP and RP conditions cis isomers were more weakly retained than the corresponding trans isomers. The only exception to this was the chromatographic behavior of C(24) methyl esters. It was established that increasing the polarity of substituents at C(24) and C(24a) led to stronger retention in NP systems, i.e. weaker retention in RP systems. Highly selective separation was achieved in all the chromatographic systems investigated. Possible separation mechanisms are discussed on the basis of the results obtained.
T2  - Journal of Planar Chromatography - Modern TLC
T1  - Planar chromatography of cholic acid-derived cis-trans isomeric bis-steroidal tetraoxanes
VL  - 22
IS  - 3
SP  - 175
EP  - 181
DO  - 10.1556/JPC.22.2009.3.3
ER  - 

@article{
author = "Šegan, Sandra and Opsenica, Dejan and Šolaja, Bogdan and Milojković-Opsenica, Dušanka",
year = "2009",
abstract = "Seven pairs of cis-trans isomers of bis-steroidal tetraoxanes have been examined by both normal-phase (NP) and reversed-phase (RP) planar chromatography. Unmodified silica gel was used with ethyl acetate-toluene and ethyl acetate-petroleum ether as mobile phases in typical normal-phase systems. CN-silica with the mobile phases methanol-water and acetone-water and RP-18 silica with water-organic modifier (methanol, acetone, or dioxane) mobile phases were used as reversed-phase systems. For the RP systems a good linear correlation was established between R M values and amount ([%] ν/ν ) of organic modifier in the mobile phase (usually r > 0.99). It was found that under both NP and RP conditions cis isomers were more weakly retained than the corresponding trans isomers. The only exception to this was the chromatographic behavior of C(24) methyl esters. It was established that increasing the polarity of substituents at C(24) and C(24a) led to stronger retention in NP systems, i.e. weaker retention in RP systems. Highly selective separation was achieved in all the chromatographic systems investigated. Possible separation mechanisms are discussed on the basis of the results obtained.",
journal = "Journal of Planar Chromatography - Modern TLC",
title = "Planar chromatography of cholic acid-derived cis-trans isomeric bis-steroidal tetraoxanes",
volume = "22",
number = "3",
pages = "175-181",
doi = "10.1556/JPC.22.2009.3.3"
}

Šegan, S., Opsenica, D., Šolaja, B.,& Milojković-Opsenica, D.. (2009). Planar chromatography of cholic acid-derived cis-trans isomeric bis-steroidal tetraoxanes. in Journal of Planar Chromatography - Modern TLC, 22(3), 175-181.
https://doi.org/10.1556/JPC.22.2009.3.3

Šegan S, Opsenica D, Šolaja B, Milojković-Opsenica D. Planar chromatography of cholic acid-derived cis-trans isomeric bis-steroidal tetraoxanes. in Journal of Planar Chromatography - Modern TLC. 2009;22(3):175-181.
doi:10.1556/JPC.22.2009.3.3 .

Šegan, Sandra, Opsenica, Dejan, Šolaja, Bogdan, Milojković-Opsenica, Dušanka, "Planar chromatography of cholic acid-derived cis-trans isomeric bis-steroidal tetraoxanes" in Journal of Planar Chromatography - Modern TLC, 22, no. 3 (2009):175-181,
https://doi.org/10.1556/JPC.22.2009.3.3 . .

TY  - JOUR
AU  - Opsenica, Dejan
AU  - Šolaja, Bogdan
PY  - 2009
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/520
AB  - The problem of endemic malaria continues unabated globally. Malaria affects 40 % of the global population, causing an estimated annual mortality of 1.5-2.7 million people. The World Health Organization (WHO) estimates that 90 % of these deaths occur in sub-Saharan Africa among infants under the age of five. While a vaccine against malaria continues to be elusive, chemotherapy remains the most viable alternative towards treatment of the disease. During last years, the situation has become urgent in many ways, but mainly because of the development of chloroquine-resistant (CQR) strains of Plasmodium falciparum (Pf). The discovery that artemisinin (ART, 1), an active principle of Artemisia annua L., expresses a significant antimalarial activity, especially against CQR strains, opened new approaches for combating malaria. Since the early 1980s, hundreds of semi-synthetic and synthetic peroxides have been developed and tested for their antimalarial activity, the results of which were extensively reviewed. In addition, in therapeutic practice, there is no reported case of drug resistance to these antimalarial peroxides. This review summarizes recent achievements in the area of peroxide drug development for malaria chemotherapy.
AB  - Širenje malarije je stalno prisutan problem na globalnom nivou. Od malarije godišnje oboli 40 % svetske populacije i oko 1,5-2,7 miliona ljudi umre. Prema podacima Svetske zdravstvene organizacije, 90 % smrtnih slučajeva je u zemljama podsaharske Afrike, među kojima dominiraju deca starosti do 5 godina. Usled nemogućnosti razvoja vakcine, hemoterapija ostaje kao jedini pouzdan oblik lečenja od ove bolesti. Poslednjih godina problem borbe protiv malarije postaje urgentan iz brojnih razloga, među kojima je najznačajniji razvoj hlorokin-rezistentnih sojeva parazita. Otkriće da artemizinin (ART, 1) i njegovi derivati pokazuju izuzetnu efikasnost prema hlorokin-rezistentnim sojevima otvorilo je velike mogućnosti u borbi protiv malarije. Od tada, posebno tokom 80-tih godina, sintetisan je veliki broj jedinjenja i rezultati njihove aktivnosti opisani su u mnogim naučnim publikacijama. Osim toga, u kliničkoj praksi nisu zabeleženi primeri pojave rezistencije parazita prema ovoj klasi antimalarika. U ovom revijalnom radu opisani su najnoviji rezultati u razvoju peroksidnih antimalarika.
PB  - Serbian Chemical Soc, Belgrade
T2  - Journal of the Serbian Chemical Society
T1  - Antimalarial peroxides
T1  - Peroksidni antimalarici
VL  - 74
IS  - 11
SP  - 1155
EP  - 1193
DO  - 10.2298/JSC0911155O
ER  - 

@article{
author = "Opsenica, Dejan and Šolaja, Bogdan",
year = "2009",
abstract = "The problem of endemic malaria continues unabated globally. Malaria affects 40 % of the global population, causing an estimated annual mortality of 1.5-2.7 million people. The World Health Organization (WHO) estimates that 90 % of these deaths occur in sub-Saharan Africa among infants under the age of five. While a vaccine against malaria continues to be elusive, chemotherapy remains the most viable alternative towards treatment of the disease. During last years, the situation has become urgent in many ways, but mainly because of the development of chloroquine-resistant (CQR) strains of Plasmodium falciparum (Pf). The discovery that artemisinin (ART, 1), an active principle of Artemisia annua L., expresses a significant antimalarial activity, especially against CQR strains, opened new approaches for combating malaria. Since the early 1980s, hundreds of semi-synthetic and synthetic peroxides have been developed and tested for their antimalarial activity, the results of which were extensively reviewed. In addition, in therapeutic practice, there is no reported case of drug resistance to these antimalarial peroxides. This review summarizes recent achievements in the area of peroxide drug development for malaria chemotherapy., Širenje malarije je stalno prisutan problem na globalnom nivou. Od malarije godišnje oboli 40 % svetske populacije i oko 1,5-2,7 miliona ljudi umre. Prema podacima Svetske zdravstvene organizacije, 90 % smrtnih slučajeva je u zemljama podsaharske Afrike, među kojima dominiraju deca starosti do 5 godina. Usled nemogućnosti razvoja vakcine, hemoterapija ostaje kao jedini pouzdan oblik lečenja od ove bolesti. Poslednjih godina problem borbe protiv malarije postaje urgentan iz brojnih razloga, među kojima je najznačajniji razvoj hlorokin-rezistentnih sojeva parazita. Otkriće da artemizinin (ART, 1) i njegovi derivati pokazuju izuzetnu efikasnost prema hlorokin-rezistentnim sojevima otvorilo je velike mogućnosti u borbi protiv malarije. Od tada, posebno tokom 80-tih godina, sintetisan je veliki broj jedinjenja i rezultati njihove aktivnosti opisani su u mnogim naučnim publikacijama. Osim toga, u kliničkoj praksi nisu zabeleženi primeri pojave rezistencije parazita prema ovoj klasi antimalarika. U ovom revijalnom radu opisani su najnoviji rezultati u razvoju peroksidnih antimalarika.",
publisher = "Serbian Chemical Soc, Belgrade",
journal = "Journal of the Serbian Chemical Society",
title = "Antimalarial peroxides, Peroksidni antimalarici",
volume = "74",
number = "11",
pages = "1155-1193",
doi = "10.2298/JSC0911155O"
}

Opsenica, D.,& Šolaja, B.. (2009). Antimalarial peroxides. in Journal of the Serbian Chemical Society
Serbian Chemical Soc, Belgrade., 74(11), 1155-1193.
https://doi.org/10.2298/JSC0911155O

Opsenica D, Šolaja B. Antimalarial peroxides. in Journal of the Serbian Chemical Society. 2009;74(11):1155-1193.
doi:10.2298/JSC0911155O .

Opsenica, Dejan, Šolaja, Bogdan, "Antimalarial peroxides" in Journal of the Serbian Chemical Society, 74, no. 11 (2009):1155-1193,
https://doi.org/10.2298/JSC0911155O . .

TY  - JOUR
AU  - Opsenica, Igor
AU  - Smith, Kirsten K.
AU  - Gerena, Lucia
AU  - Gaica, Sandra
AU  - Šolaja, Bogdan
PY  - 2008
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/7535
AB  - Several tetraoxane and 4-aminoquinoline molecules were prepared in
order to examine the influence of ribofuranose as a carrier molecule on the antimalarial
activity of test compounds. The synthesized compounds showed pronounced
antimalarial activity against Plasmodium falciparum chloroquine susceptible
D6, chloroquine resistant W2 and multidrug-resistant TM91C235 (Thailand)
strains. The aminoquinoline derivative 4 was more active against W2 and
TM91C235 strains than the control compounds (CQ and MFQ).
AB  - U ovom radu prikazana je sinteza nekoliko ribofuranozidnih tetraoksana i 4-aminohinolina u cilju sagledavanja odnosa struktura-aktivnost ove vrste antimalarika. Jedinjenja su pokazala izraženu antimalarijsku aktivnost prema hlorokin-osetljivom (D6), hlorokin-rezistentnom (W2) i višestruko rezistentnom (TM91C235 (Thailand)) soju Plasmodium falciparum. Aminohinolinski derivat 4 je aktivniji prema W2 i TM91C235 sojevima od kontrolnih jedinjenja (hlorokin i meflokin).
PB  - Belgrade : Serbian Chemical Society
T2  - Journal of Serbian Chemical Society
T1  - Ribofuranose as a carrier of tetraoxane and 4-aminoquinoline antimalarial pharmacophores
T1  - Ribofuranoza kao nosač tetraoksanske i 4-aminohinolinske antimalarijske farmakofore
VL  - 73
IS  - 11
SP  - 1021
EP  - 1025
DO  - 10.2298/JSC0811021О
ER  - 

@article{
author = "Opsenica, Igor and Smith, Kirsten K. and Gerena, Lucia and Gaica, Sandra and Šolaja, Bogdan",
year = "2008",
abstract = "Several tetraoxane and 4-aminoquinoline molecules were prepared in
order to examine the influence of ribofuranose as a carrier molecule on the antimalarial
activity of test compounds. The synthesized compounds showed pronounced
antimalarial activity against Plasmodium falciparum chloroquine susceptible
D6, chloroquine resistant W2 and multidrug-resistant TM91C235 (Thailand)
strains. The aminoquinoline derivative 4 was more active against W2 and
TM91C235 strains than the control compounds (CQ and MFQ)., U ovom radu prikazana je sinteza nekoliko ribofuranozidnih tetraoksana i 4-aminohinolina u cilju sagledavanja odnosa struktura-aktivnost ove vrste antimalarika. Jedinjenja su pokazala izraženu antimalarijsku aktivnost prema hlorokin-osetljivom (D6), hlorokin-rezistentnom (W2) i višestruko rezistentnom (TM91C235 (Thailand)) soju Plasmodium falciparum. Aminohinolinski derivat 4 je aktivniji prema W2 i TM91C235 sojevima od kontrolnih jedinjenja (hlorokin i meflokin).",
publisher = "Belgrade : Serbian Chemical Society",
journal = "Journal of Serbian Chemical Society",
title = "Ribofuranose as a carrier of tetraoxane and 4-aminoquinoline antimalarial pharmacophores, Ribofuranoza kao nosač tetraoksanske i 4-aminohinolinske antimalarijske farmakofore",
volume = "73",
number = "11",
pages = "1021-1025",
doi = "10.2298/JSC0811021О"
}

Opsenica, I., Smith, K. K., Gerena, L., Gaica, S.,& Šolaja, B.. (2008). Ribofuranose as a carrier of tetraoxane and 4-aminoquinoline antimalarial pharmacophores. in Journal of Serbian Chemical Society
Belgrade : Serbian Chemical Society., 73(11), 1021-1025.
https://doi.org/10.2298/JSC0811021О

Opsenica I, Smith KK, Gerena L, Gaica S, Šolaja B. Ribofuranose as a carrier of tetraoxane and 4-aminoquinoline antimalarial pharmacophores. in Journal of Serbian Chemical Society. 2008;73(11):1021-1025.
doi:10.2298/JSC0811021О .

Opsenica, Igor, Smith, Kirsten K., Gerena, Lucia, Gaica, Sandra, Šolaja, Bogdan, "Ribofuranose as a carrier of tetraoxane and 4-aminoquinoline antimalarial pharmacophores" in Journal of Serbian Chemical Society, 73, no. 11 (2008):1021-1025,
https://doi.org/10.2298/JSC0811021О . .

TY  - JOUR
AU  - Opsenica, Igor
AU  - Opsenica, Dejan
AU  - Lanteri, C.A.
AU  - Anova, L.
AU  - Milhous, Wilbur K.
AU  - Smith, K. S.
AU  - Šolaja, Bogdan
PY  - 2008
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/448
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 >960 mg/kg.
PB  - American Chemical Society (ACS)
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 and Lanteri, C.A. and Anova, L. and Milhous, Wilbur K. and Smith, K. S. and Šolaja, Bogdan",
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 >960 mg/kg.",
publisher = "American Chemical Society (ACS)",
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., Lanteri, C.A., Anova, L., Milhous, W. K., Smith, K. S.,& Šolaja, B.. (2008). New chimeric antimalarials with 4-aminoquinoline moiety linked to a tetraoxane skeleton. in Journal of Medicinal Chemistry
American Chemical Society (ACS)., 51(19), 6216-6219.
https://doi.org/10.1021/jm8006905

Opsenica I, Opsenica D, Lanteri C, Anova L, Milhous WK, Smith KS, Šolaja B. 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, Lanteri, C.A., Anova, L., Milhous, Wilbur K., Smith, K. S., Šolaja, Bogdan, "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  - Śolaja, B.A.
AU  - Opsenica, Dejan
AU  - Smith, K. S.
AU  - Milhous, Wilbur K.
AU  - Terzić, Nataša
AU  - Opsenica, Igor
AU  - Burnett, J.C.
AU  - Nuss, J.
AU  - Gussio, R.
AU  - Bavari, S.
PY  - 2008
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/451
AB  - We report on the initial result of the coupling of 4-amino-7- 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 micromolar levels (7-31 μM). Interestingly, structural features imparting increased antimalarial activity also provide increased metalloprotease inhibition, thus allowing for simultaneous compound optimizations against distinct targets.
PB  - American Chemical Society (ACS)
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 = "Śolaja, B.A. and Opsenica, Dejan and Smith, K. S. and Milhous, Wilbur K. and Terzić, Nataša and Opsenica, Igor and Burnett, J.C. and Nuss, J. and Gussio, R. and Bavari, S.",
year = "2008",
abstract = "We report on the initial result of the coupling of 4-amino-7- 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 micromolar levels (7-31 μM). Interestingly, structural features imparting increased antimalarial activity also provide increased metalloprotease inhibition, thus allowing for simultaneous compound optimizations against distinct targets.",
publisher = "American Chemical Society (ACS)",
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"
}

Śolaja, B.A., Opsenica, D., Smith, K. S., Milhous, W. K., Terzić, 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
American Chemical Society (ACS)., 51(15), 4388-4391.
https://doi.org/10.1021/jm800737y

Śolaja B, Opsenica D, Smith KS, Milhous WK, Terzić N, Opsenica I, Burnett J, 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 .

Śolaja, B.A., Opsenica, Dejan, Smith, K. S., Milhous, Wilbur K., Terzić, Nataša, Opsenica, Igor, Burnett, J.C., 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, 51, no. 15 (2008):4388-4391,
https://doi.org/10.1021/jm800737y . .

TY  - JOUR
AU  - Opsenica, Igor
AU  - Opsenica, Dejan
AU  - Smith, K. S.
AU  - Milhous, Wilbur K.
AU  - Šolaja, Bogdan
PY  - 2008
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/471
AB  - Of 17 prepared 1,2,4,5-tetraoxacyclohexanes stable to reductive and acidic conditions, 3 of them were more active than artemisinin against CQ and MFQ resistant strain TM91C235 and all compounds were more active in vitro against W2 than against D6 strain. In vivo, amines 10 and 11a cured all mice at higher doses with MCD ≤ 37.5 (mg/kg)/day. Triol 13 was exceptionally active against melanoma (LOX IMVI) and ovarian cancer (IGROV1), both with LC 50 = 60 nM.
PB  - American Chemical Society (ACS)
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 and Smith, K. S. and Milhous, Wilbur K. and Šolaja, Bogdan",
year = "2008",
abstract = "Of 17 prepared 1,2,4,5-tetraoxacyclohexanes stable to reductive and acidic conditions, 3 of them were more active than artemisinin against CQ and MFQ resistant strain TM91C235 and all compounds were more active in vitro against W2 than against D6 strain. In vivo, amines 10 and 11a cured all mice at higher doses with MCD ≤ 37.5 (mg/kg)/day. Triol 13 was exceptionally active against melanoma (LOX IMVI) and ovarian cancer (IGROV1), both with LC 50 = 60 nM.",
publisher = "American Chemical Society (ACS)",
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., Smith, K. S., Milhous, W. K.,& Šolaja, B.. (2008). Chemical stability of the peroxide bond enables diversified synthesis of potent tetraoxane antimalarials. in Journal of Medicinal Chemistry
American Chemical Society (ACS)., 51(7), 2261-2266.
https://doi.org/10.1021/jm701417a

Opsenica I, Opsenica D, Smith KS, Milhous WK, Šolaja B. 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, Smith, K. S., Milhous, Wilbur K., Šolaja, Bogdan, "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  - Opsenica, Dejan
AU  - Terzić-Jovanović, Nataša
AU  - Smith, P.L.
AU  - Yang, Y.
AU  - Anova, L.
AU  - Smith, K. S.
AU  - Šolaja, Bogdan
PY  - 2008
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/444
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 ≤ 20 mg/kg/day. The diol 13 was most potent antiproliferative with GI50, TGI, LC50 MG_MID 0.98 μM, 3.80 μM, 11.22 μM, respectively. All tested compounds showed no toxic effects.
PB  - Oxford : Pergamon-Elsevier Science Ltd
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 and Terzić-Jovanović, Nataša and Smith, P.L. and Yang, Y. and Anova, L. and Smith, K. S. and Šolaja, Bogdan",
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 ≤ 20 mg/kg/day. The diol 13 was most potent antiproliferative with GI50, TGI, LC50 MG_MID 0.98 μM, 3.80 μM, 11.22 μM, respectively. All tested compounds showed no toxic effects.",
publisher = "Oxford : Pergamon-Elsevier Science Ltd",
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., Terzić-Jovanović, N., Smith, P.L., Yang, Y., Anova, L., Smith, K. S.,& Šolaja, B.. (2008). Mixed tetraoxanes containing the acetone subunit as antimalarials. in Bioorganic and Medicinal Chemistry
Oxford : Pergamon-Elsevier Science Ltd., 16(14), 7039-7045.
https://doi.org/10.1016/j.bmc.2008.05.017

Opsenica D, Terzić-Jovanović N, Smith P, Yang Y, Anova L, Smith KS, Šolaja B. 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, Terzić-Jovanović, Nataša, Smith, P.L., Yang, Y., Anova, L., Smith, K. S., Šolaja, Bogdan, "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  - Opsenica, Igor
AU  - Opsenica, Dejan
AU  - Jadranin, Milka
AU  - Smith, Kirsten
AU  - Milhous, Wilbur K.
AU  - Stratakis, Manolis
AU  - Šolaja, Bogdan
PY  - 2007
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/303
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 Society
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 and Jadranin, Milka and Smith, Kirsten and Milhous, Wilbur K. and Stratakis, Manolis and Šolaja, Bogdan",
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 Society",
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., Jadranin, M., Smith, K., Milhous, W. K., Stratakis, M.,& Šolaja, B.. (2007). On peroxide antimalarials. in Journal of the Serbian Chemical Society
Serbian Chemical Society., 72(12), 1181-1190.
https://doi.org/10.2298/JSC0712181O

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

Opsenica, Igor, Opsenica, Dejan, Jadranin, Milka, Smith, Kirsten, Milhous, Wilbur K., Stratakis, Manolis, Šolaja, Bogdan, "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  - Terzić-Jovanović, Nataša
AU  - Opsenica, Dejan
AU  - Milić, Dragana
AU  - Tinant, Bernard
AU  - Smith, K. S.
AU  - Milhous, Wilbur K.
AU  - Šolaja, Bogdan
PY  - 2007
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/350
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 >960 mg/kg), respectively, and they were extremely active against melanoma LOX IMVI cancer, LC50 = 22 nM and 69 nM, respectively.
PB  - American Chemical Society (ACS)
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 and Milić, Dragana and Tinant, Bernard and Smith, K. S. and Milhous, Wilbur K. and Šolaja, Bogdan",
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 >960 mg/kg), respectively, and they were extremely active against melanoma LOX IMVI cancer, LC50 = 22 nM and 69 nM, respectively.",
publisher = "American Chemical Society (ACS)",
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., Milić, D., Tinant, B., Smith, K. S., Milhous, W. K.,& Šolaja, B.. (2007). Deoxycholic acid-derived tetraoxane antimalarials and antiproliferatives. in Journal of Medicinal Chemistry
American Chemical Society (ACS)., 50(21), 5118-5127.
https://doi.org/10.1021/jm070684m

Terzić-Jovanović N, Opsenica D, Milić D, Tinant B, Smith KS, Milhous WK, Šolaja B. 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, Milić, Dragana, Tinant, Bernard, Smith, K. S., Milhous, Wilbur K., Šolaja, Bogdan, "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  - Burnett, J.C.
AU  - Opsenica, Dejan
AU  - Sriraghavan, K.
AU  - Panchal, R.G.
AU  - Ruthel, G.
AU  - Hermone, A.R.
AU  - Nguyen, T.L.
AU  - Kenny, T.A.
AU  - Lane, D.J.
AU  - McGrath, C.F.
AU  - Schmidt, J.J.
AU  - Vennerstrom, J.L.
AU  - Gussio, R.
AU  - Šolaja, Bogdan
AU  - Bavari, S.
PY  - 2007
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/361
AB  - We previously identified structurally diverse small molecule (non-peptidic) inhibitors (SMNPIs) of the botulinum neurotoxin serotype A (BoNT/A) light chain (LC). Of these, several (including antimalarial drugs) contained a 4-amino-7-chloroquinoline (ACQ) substructure and a separate positive ionizable amine component. The same antimalarials have also been found to interfere with BoNT/A translocation into neurons, via pH elevation of the toxin-mediated endosome. Thus, this structural class of small molecules may serve as dual-function BoNT/A inhibitors. In this study, we used a refined pharmacophore for BoNT/A LC inhibition to identify four new, potent inhibitors of this structural class (IC50's ranged from 3.2 to 17 μM). Molecular docking indicated that the binding modes for the new SMNPIs are consistent with those of other inhibitors that we have identified, further supporting our structure-based pharmacophore. Finally, structural motifs of the new SMNPIs, as well as two structure-based derivatives, were examined for activity, providing valuable information about pharmacophore component contributions to inhibition.
PB  - American Chemical Society (ACS)
T2  - Journal of Medicinal Chemistry
T1  - A refined pharmacophore identifies potent 4-amino-7-chloroquinoline-based inhibitors of the botulinum neurotoxin serotype A metalloprotease
VL  - 50
IS  - 9
SP  - 2127
EP  - 2136
DO  - 10.1021/jm061446e
ER  - 

@article{
author = "Burnett, J.C. and Opsenica, Dejan and Sriraghavan, K. and Panchal, R.G. and Ruthel, G. and Hermone, A.R. and Nguyen, T.L. and Kenny, T.A. and Lane, D.J. and McGrath, C.F. and Schmidt, J.J. and Vennerstrom, J.L. and Gussio, R. and Šolaja, Bogdan and Bavari, S.",
year = "2007",
abstract = "We previously identified structurally diverse small molecule (non-peptidic) inhibitors (SMNPIs) of the botulinum neurotoxin serotype A (BoNT/A) light chain (LC). Of these, several (including antimalarial drugs) contained a 4-amino-7-chloroquinoline (ACQ) substructure and a separate positive ionizable amine component. The same antimalarials have also been found to interfere with BoNT/A translocation into neurons, via pH elevation of the toxin-mediated endosome. Thus, this structural class of small molecules may serve as dual-function BoNT/A inhibitors. In this study, we used a refined pharmacophore for BoNT/A LC inhibition to identify four new, potent inhibitors of this structural class (IC50's ranged from 3.2 to 17 μM). Molecular docking indicated that the binding modes for the new SMNPIs are consistent with those of other inhibitors that we have identified, further supporting our structure-based pharmacophore. Finally, structural motifs of the new SMNPIs, as well as two structure-based derivatives, were examined for activity, providing valuable information about pharmacophore component contributions to inhibition.",
publisher = "American Chemical Society (ACS)",
journal = "Journal of Medicinal Chemistry",
title = "A refined pharmacophore identifies potent 4-amino-7-chloroquinoline-based inhibitors of the botulinum neurotoxin serotype A metalloprotease",
volume = "50",
number = "9",
pages = "2127-2136",
doi = "10.1021/jm061446e"
}

Burnett, J.C., Opsenica, D., Sriraghavan, K., Panchal, R.G., Ruthel, G., Hermone, A.R., Nguyen, T.L., Kenny, T.A., Lane, D.J., McGrath, C.F., Schmidt, J.J., Vennerstrom, J.L., Gussio, R., Šolaja, B.,& Bavari, S.. (2007). A refined pharmacophore identifies potent 4-amino-7-chloroquinoline-based inhibitors of the botulinum neurotoxin serotype A metalloprotease. in Journal of Medicinal Chemistry
American Chemical Society (ACS)., 50(9), 2127-2136.
https://doi.org/10.1021/jm061446e

Burnett J, Opsenica D, Sriraghavan K, Panchal R, Ruthel G, Hermone A, Nguyen T, Kenny T, Lane D, McGrath C, Schmidt J, Vennerstrom J, Gussio R, Šolaja B, Bavari S. A refined pharmacophore identifies potent 4-amino-7-chloroquinoline-based inhibitors of the botulinum neurotoxin serotype A metalloprotease. in Journal of Medicinal Chemistry. 2007;50(9):2127-2136.
doi:10.1021/jm061446e .

Burnett, J.C., Opsenica, Dejan, Sriraghavan, K., Panchal, R.G., Ruthel, G., Hermone, A.R., Nguyen, T.L., Kenny, T.A., Lane, D.J., McGrath, C.F., Schmidt, J.J., Vennerstrom, J.L., Gussio, R., Šolaja, Bogdan, Bavari, S., "A refined pharmacophore identifies potent 4-amino-7-chloroquinoline-based inhibitors of the botulinum neurotoxin serotype A metalloprotease" in Journal of Medicinal Chemistry, 50, no. 9 (2007):2127-2136,
https://doi.org/10.1021/jm061446e . .

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 . .