TY  - JOUR
AU  - Cvijetić, Ilija
AU  - Žižak, Željko S.
AU  - Stanojković, Tatjana
AU  - Juranić, Zorica D.
AU  - Terzić-Jovanović, Nataša
AU  - Opsenica, Igor
AU  - Opsenica, Dejan M.
AU  - Juranić, Ivan O.
AU  - Drakulić, Branko J.
PY  - 2010
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/1120
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. (C) 2010 Elsevier Masson SAS. All rights reserved.
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 S. and Stanojković, Tatjana and Juranić, Zorica D. and Terzić-Jovanović, Nataša and Opsenica, Igor and Opsenica, Dejan M. and Juranić, Ivan O. and Drakulić, Branko J.",
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. (C) 2010 Elsevier Masson SAS. All rights reserved.",
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. S., Stanojković, T., Juranić, Z. D., Terzić-Jovanović, N., Opsenica, I., Opsenica, D. M., Juranić, I. O.,& Drakulić, B. J.. (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 ŽS, Stanojković T, Juranić ZD, Terzić-Jovanović N, Opsenica I, Opsenica DM, Juranić IO, Drakulić BJ. 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 S., Stanojković, Tatjana, Juranić, Zorica D., Terzić-Jovanović, Nataša, Opsenica, Igor, Opsenica, Dejan M., Juranić, Ivan O., Drakulić, Branko J., "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  - Šegan, Sandra B.
AU  - Opsenica, Dejan M.
AU  - Šolaja, Bogdan A.
AU  - Milojković-Opsenica, Dušanka
PY  - 2009
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/995
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 ([%] v/v) of organic modifier in the mobile phase (usually r  gt  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.
PB  - Research Inst Medicinal Plants, Budakalasz
T2  - Journal of Planar Chromatography: Modern TLC / Thin Layer Chromatography
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 B. and Opsenica, Dejan M. and Šolaja, Bogdan A. 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 ([%] v/v) of organic modifier in the mobile phase (usually r  gt  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.",
publisher = "Research Inst Medicinal Plants, Budakalasz",
journal = "Journal of Planar Chromatography: Modern TLC / Thin Layer Chromatography",
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. B., Opsenica, D. M., Šolaja, B. A.,& Milojković-Opsenica, D.. (2009). Planar Chromatography of Cholic Acid-Derived cis-trans Isomeric bis-Steroidal Tetraoxanes. in Journal of Planar Chromatography: Modern TLC / Thin Layer Chromatography
Research Inst Medicinal Plants, Budakalasz., 22(3), 175-181.
https://doi.org/10.1556/JPC.22.2009.3.3

Šegan SB, Opsenica DM, Šolaja BA, Milojković-Opsenica D. Planar Chromatography of Cholic Acid-Derived cis-trans Isomeric bis-Steroidal Tetraoxanes. in Journal of Planar Chromatography: Modern TLC / Thin Layer Chromatography. 2009;22(3):175-181.
doi:10.1556/JPC.22.2009.3.3 .

Šegan, Sandra B., Opsenica, Dejan M., Šolaja, Bogdan A., Milojković-Opsenica, Dušanka, "Planar Chromatography of Cholic Acid-Derived cis-trans Isomeric bis-Steroidal Tetraoxanes" in Journal of Planar Chromatography: Modern TLC / Thin Layer Chromatography, 22, no. 3 (2009):175-181,
https://doi.org/10.1556/JPC.22.2009.3.3 . .

TY  - JOUR
AU  - Opsenica, Dejan M.
AU  - Šolaja, Bogdan A.
PY  - 2009
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/1033
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 M. and Šolaja, Bogdan A.",
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. M.,& Šolaja, B. A.. (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 DM, Šolaja BA. Antimalarial peroxides. in Journal of the Serbian Chemical Society. 2009;74(11):1155-1193.
doi:10.2298/JSC0911155O .

Opsenica, Dejan M., Šolaja, Bogdan A., "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  - 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  - Smith, Kirsten K.
AU  - Gerena, Lucia
AU  - Gaica, Sandra
AU  - Šolaja, Bogdan A.
PY  - 2008
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/587
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  - Serbian Chemical Soc, Belgrade
T2  - Journal of the 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/JSC0811021O
ER  - 

@article{
author = "Opsenica, Igor and Smith, Kirsten K. and Gerena, Lucia and Gaica, Sandra and Šolaja, Bogdan A.",
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 = "Serbian Chemical Soc, Belgrade",
journal = "Journal of the 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/JSC0811021O"
}

Opsenica, I., Smith, K. K., Gerena, L., Gaica, S.,& Šolaja, B. A.. (2008). Ribofuranose as a carrier of tetraoxane and 4-aminoquinoline antimalarial pharmacophores. in Journal of the Serbian Chemical Society
Serbian Chemical Soc, Belgrade., 73(11), 1021-1025.
https://doi.org/10.2298/JSC0811021O

Opsenica I, Smith KK, Gerena L, Gaica S, Šolaja BA. Ribofuranose as a carrier of tetraoxane and 4-aminoquinoline antimalarial pharmacophores. in Journal of the Serbian Chemical Society. 2008;73(11):1021-1025.
doi:10.2298/JSC0811021O .

Opsenica, Igor, Smith, Kirsten K., Gerena, Lucia, Gaica, Sandra, Šolaja, Bogdan A., "Ribofuranose as a carrier of tetraoxane and 4-aminoquinoline antimalarial pharmacophores" in Journal of the Serbian Chemical Society, 73, no. 11 (2008):1021-1025,
https://doi.org/10.2298/JSC0811021O . .

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  - Burnett, James C.
AU  - Opsenica, Dejan M.
AU  - Sriraghavan, Kamaraj
AU  - Panchal, Rekha G.
AU  - Ruthel, Gordon
AU  - Hermone, Ann R.
AU  - Nguyen, Tam L.
AU  - Kenny, Tara A.
AU  - Lane, Douglas J.
AU  - McGrath, Connor F.
AU  - Schmidt, James J.
AU  - Vennerstrom, Jonathan L.
AU  - Gussio, Rick
AU  - Šolaja, Bogdan A.
AU  - Bavari, Sina
PY  - 2007
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/828
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 (IC(50)'s ranged from 3.2 to 17 mu M). 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  - Amer Chemical Soc, Washington
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, James C. and Opsenica, Dejan M. and Sriraghavan, Kamaraj and Panchal, Rekha G. and Ruthel, Gordon and Hermone, Ann R. and Nguyen, Tam L. and Kenny, Tara A. and Lane, Douglas J. and McGrath, Connor F. and Schmidt, James J. and Vennerstrom, Jonathan L. and Gussio, Rick and Šolaja, Bogdan A. and Bavari, Sina",
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 (IC(50)'s ranged from 3.2 to 17 mu M). 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 = "Amer Chemical Soc, Washington",
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. M., 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. A.,& 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
Amer Chemical Soc, Washington., 50(9), 2127-2136.
https://doi.org/10.1021/jm061446e

Burnett JC, Opsenica DM, Sriraghavan K, Panchal RG, Ruthel G, Hermone AR, Nguyen TL, Kenny TA, Lane DJ, McGrath CF, Schmidt JJ, Vennerstrom JL, Gussio R, Šolaja BA, 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, James C., Opsenica, Dejan M., Sriraghavan, Kamaraj, Panchal, Rekha G., Ruthel, Gordon, Hermone, Ann R., Nguyen, Tam L., Kenny, Tara A., Lane, Douglas J., McGrath, Connor F., Schmidt, James J., Vennerstrom, Jonathan L., Gussio, Rick, Šolaja, Bogdan A., Bavari, Sina, "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  - 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 . .