Smith, K. S.

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aca9e464-fb37-436d-ae8d-302fd3c73d1e
  • Smith, K. S. (6)
  • Smith, Kirsten (1)
  • Smith, Kirsten S. (1)
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Author's Bibliography

New chimeric antimalarials with 4-aminoquinoline moiety linked to a tetraoxane skeleton

Opsenica, Igor; Opsenica, Dejan; Lanteri, C.A.; Anova, L.; Milhous, Wilbur K.; Smith, K. S.; Šolaja, Bogdan

(American Chemical Society (ACS), 2008)

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 . .
58
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67

Novel 4-aminoquinolines active against chloroquine-resistant and sensitive P. falciparum strains that also inhibit botulinum serotype A

Śolaja, B.A.; Opsenica, Dejan; Smith, K. S.; Milhous, Wilbur K.; Terzić, Nataša; Opsenica, Igor; Burnett, J.C.; Nuss, J.; Gussio, R.; Bavari, S.

(American Chemical Society (ACS), 2008)

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 . .
3
46
46
52

Chemical stability of the peroxide bond enables diversified synthesis of potent tetraoxane antimalarials

Opsenica, Igor; Opsenica, Dejan; Smith, K. S.; Milhous, Wilbur K.; Šolaja, Bogdan

(American Chemical Society (ACS), 2008)

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 . .
3
62
57
65

Mixed tetraoxanes containing the acetone subunit as antimalarials

Opsenica, Dejan; Terzić-Jovanović, Nataša; Smith, P.L.; Yang, Y.; Anova, L.; Smith, K. S.; Šolaja, Bogdan

(Oxford : Pergamon-Elsevier Science Ltd, 2008)

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 . .
16
15
17

On peroxide antimalarials

Opsenica, Igor; Opsenica, Dejan; Jadranin, Milka; Smith, Kirsten; Milhous, Wilbur K.; Stratakis, Manolis; Šolaja, Bogdan

(Serbian Chemical Society, 2007)

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 . .
10
6
9

Deoxycholic acid-derived tetraoxane antimalarials and antiproliferatives

Terzić-Jovanović, Nataša; Opsenica, Dejan; Milić, Dragana; Tinant, Bernard; Smith, K. S.; Milhous, Wilbur K.; Šolaja, Bogdan

(American Chemical Society (ACS), 2007)

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 . .
65
72
80

Tetraoxane antimalarials and their reaction with Fe(II)

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

(American Chemical Society (ACS), 2006)

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 . .
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Reductive cleavage of 1,2,4,5-tetraoxane antimalarials

Šolaja, Bogdan; Terzić, Nataša; Smith, K. S.; Opsenica, Dejan; Smith, PL; Milhous, Wilbur K.

(American Chemical Society (ACS), 2005)

TY  - CONF
AU  - Šolaja, Bogdan
AU  - Terzić, Nataša
AU  - Smith, K. S.
AU  - Opsenica, Dejan
AU  - Smith, PL
AU  - Milhous, Wilbur K.
PY  - 2005
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/2836
PB  - American Chemical Society (ACS)
C3  - Abstracts of papers of the American Chemical Society
T1  - Reductive cleavage of 1,2,4,5-tetraoxane antimalarials
VL  - 230
UR  - https://hdl.handle.net/21.15107/rcub_cherry_774
ER  - 
@conference{
author = "Šolaja, Bogdan and Terzić, Nataša and Smith, K. S. and Opsenica, Dejan and Smith, PL and Milhous, Wilbur K.",
year = "2005",
publisher = "American Chemical Society (ACS)",
journal = "Abstracts of papers of the American Chemical Society",
title = "Reductive cleavage of 1,2,4,5-tetraoxane antimalarials",
volume = "230",
url = "https://hdl.handle.net/21.15107/rcub_cherry_774"
}
Šolaja, B., Terzić, N., Smith, K. S., Opsenica, D., Smith, P.,& Milhous, W. K.. (2005). Reductive cleavage of 1,2,4,5-tetraoxane antimalarials. in Abstracts of papers of the American Chemical Society
American Chemical Society (ACS)., 230.
https://hdl.handle.net/21.15107/rcub_cherry_774
Šolaja B, Terzić N, Smith KS, Opsenica D, Smith P, Milhous WK. Reductive cleavage of 1,2,4,5-tetraoxane antimalarials. in Abstracts of papers of the American Chemical Society. 2005;230.
https://hdl.handle.net/21.15107/rcub_cherry_774 .
Šolaja, Bogdan, Terzić, Nataša, Smith, K. S., Opsenica, Dejan, Smith, PL, Milhous, Wilbur K., "Reductive cleavage of 1,2,4,5-tetraoxane antimalarials" in Abstracts of papers of the American Chemical Society, 230 (2005),
https://hdl.handle.net/21.15107/rcub_cherry_774 .