Examination of the antimalarial potential of experimental aminoquinolines: poor in vitro effect does not preclude in vivo efficacy
Аутори
Srbljanović, JelenaŠtajner, Tijana
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Konstantinović, Jelena M.
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Terzić-Jovanović, Nataša
![](/themes/MirageCherry/images/orcid.png)
Uzelac, Aleksandra
Bobić, Branko
Šolaja, Bogdan A.
![](/themes/MirageCherry/images/orcid.png)
Đurković-Đaković, Olgica
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Чланак у часопису (Рецензирана верзија)
Метаподаци
Приказ свих података о документуАпстракт
Malaria remains a major disease in the developing world and globally is the most important parasitic disease causing significant morbidity and mortality. Because of widespread resistance to conventional antimalarials, including chloroquine (CQ), new drugs are urgently needed. Here we report on the antimalarial efficacy, both in vitro and in vivo, of a series of aminoquinoline derivatives with adamantane or benzothiophene as a carrier. In vitro efficacy was evaluated by a lactate dehydrogenase (LDH) assay in cultures of a CQ-sensitive (3D7) and CQ-resistant (Dd2) strain of Plasmodium falcipanim. Of a series of 26 screened compounds, 12 that exerted a growth inhibition rate of gt = 5% were further examined in vitro to determine the 50% inhibitory concentration (IC50) values. Nine compounds shown in preliminary experiments to be non-toxic in vivo were evaluated in C57BL/6 mice infected with Plasmodium herghei ANKA strain using a modified Thompson test. All nine compounds examined in vivo... prolonged the survival of treated versus untreated mice, four of which afforded gt = 60% survival. Most notably, two of these compounds, both with the adamantane carrier, afforded complete cure (100% survival and parasite clearance). Interestingly, one of these compounds had no in vitro effect against the CQ resistant P. falciparum strain. Better in vivo compared with in vitro results suggest a role for compound metabolites rather than the compounds themselves. The results presented here point to adamantane as a carrier that enhances the antimalarial potential of aminoquinolines.
Кључне речи:
Adamantane / Aminoquinolines / LDH assay / Malaria / Thompson testИзвор:
International Journal of Antimicrobial Agents, 2017, 50, 3, 461-466Издавач:
- Elsevier Science Bv, Amsterdam
Финансирање / пројекти:
- Контрола инфекција апикомплексним патогенима: од нових места деловања лека до предикције (RS-MESTD-Integrated and Interdisciplinary Research (IIR or III)-41019)
- Синтеза аминохинолина и њихових деривата као антималарика и инхибитора ботулинум неуротоксина А (RS-MESTD-Basic Research (BR or ON)-172008)
Напомена:
- This is the peer-reviewed version of the following article: Srbljanović, J.; Štajner, T.; Konstantinović, J.; Terzić-Jovanović, N.; Uzelac, A.; Bobić, B.; Šolaja, B. A.; Djurković-Djaković, O. Examination of the Antimalarial Potential of Experimental Aminoquinolines: Poor in Vitro Effect Does Not Preclude in Vivo Efficacy. International Journal of Antimicrobial Agents 2017, 50 (3), 461–466. https://doi.org/10.1016/j.ijantimicag.2017.06.002
DOI: 10.1016/j.ijantimicag.2017.06.002
ISSN: 0924-8579
WoS: 000408686800025
Scopus: 2-s2.0-85026397158
Колекције
Институција/група
Hemijski fakultet / Faculty of ChemistryTY - JOUR AU - Srbljanović, Jelena AU - Štajner, Tijana AU - Konstantinović, Jelena M. AU - Terzić-Jovanović, Nataša AU - Uzelac, Aleksandra AU - Bobić, Branko AU - Šolaja, Bogdan A. AU - Đurković-Đaković, Olgica PY - 2017 UR - https://cherry.chem.bg.ac.rs/handle/123456789/3214 AB - Malaria remains a major disease in the developing world and globally is the most important parasitic disease causing significant morbidity and mortality. Because of widespread resistance to conventional antimalarials, including chloroquine (CQ), new drugs are urgently needed. Here we report on the antimalarial efficacy, both in vitro and in vivo, of a series of aminoquinoline derivatives with adamantane or benzothiophene as a carrier. In vitro efficacy was evaluated by a lactate dehydrogenase (LDH) assay in cultures of a CQ-sensitive (3D7) and CQ-resistant (Dd2) strain of Plasmodium falcipanim. Of a series of 26 screened compounds, 12 that exerted a growth inhibition rate of gt = 5% were further examined in vitro to determine the 50% inhibitory concentration (IC50) values. Nine compounds shown in preliminary experiments to be non-toxic in vivo were evaluated in C57BL/6 mice infected with Plasmodium herghei ANKA strain using a modified Thompson test. All nine compounds examined in vivo prolonged the survival of treated versus untreated mice, four of which afforded gt = 60% survival. Most notably, two of these compounds, both with the adamantane carrier, afforded complete cure (100% survival and parasite clearance). Interestingly, one of these compounds had no in vitro effect against the CQ resistant P. falciparum strain. Better in vivo compared with in vitro results suggest a role for compound metabolites rather than the compounds themselves. The results presented here point to adamantane as a carrier that enhances the antimalarial potential of aminoquinolines. PB - Elsevier Science Bv, Amsterdam T2 - International Journal of Antimicrobial Agents T1 - Examination of the antimalarial potential of experimental aminoquinolines: poor in vitro effect does not preclude in vivo efficacy VL - 50 IS - 3 SP - 461 EP - 466 DO - 10.1016/j.ijantimicag.2017.06.002 ER -
@article{ author = "Srbljanović, Jelena and Štajner, Tijana and Konstantinović, Jelena M. and Terzić-Jovanović, Nataša and Uzelac, Aleksandra and Bobić, Branko and Šolaja, Bogdan A. and Đurković-Đaković, Olgica", year = "2017", abstract = "Malaria remains a major disease in the developing world and globally is the most important parasitic disease causing significant morbidity and mortality. Because of widespread resistance to conventional antimalarials, including chloroquine (CQ), new drugs are urgently needed. Here we report on the antimalarial efficacy, both in vitro and in vivo, of a series of aminoquinoline derivatives with adamantane or benzothiophene as a carrier. In vitro efficacy was evaluated by a lactate dehydrogenase (LDH) assay in cultures of a CQ-sensitive (3D7) and CQ-resistant (Dd2) strain of Plasmodium falcipanim. Of a series of 26 screened compounds, 12 that exerted a growth inhibition rate of gt = 5% were further examined in vitro to determine the 50% inhibitory concentration (IC50) values. Nine compounds shown in preliminary experiments to be non-toxic in vivo were evaluated in C57BL/6 mice infected with Plasmodium herghei ANKA strain using a modified Thompson test. All nine compounds examined in vivo prolonged the survival of treated versus untreated mice, four of which afforded gt = 60% survival. Most notably, two of these compounds, both with the adamantane carrier, afforded complete cure (100% survival and parasite clearance). Interestingly, one of these compounds had no in vitro effect against the CQ resistant P. falciparum strain. Better in vivo compared with in vitro results suggest a role for compound metabolites rather than the compounds themselves. The results presented here point to adamantane as a carrier that enhances the antimalarial potential of aminoquinolines.", publisher = "Elsevier Science Bv, Amsterdam", journal = "International Journal of Antimicrobial Agents", title = "Examination of the antimalarial potential of experimental aminoquinolines: poor in vitro effect does not preclude in vivo efficacy", volume = "50", number = "3", pages = "461-466", doi = "10.1016/j.ijantimicag.2017.06.002" }
Srbljanović, J., Štajner, T., Konstantinović, J. M., Terzić-Jovanović, N., Uzelac, A., Bobić, B., Šolaja, B. A.,& Đurković-Đaković, O.. (2017). Examination of the antimalarial potential of experimental aminoquinolines: poor in vitro effect does not preclude in vivo efficacy. in International Journal of Antimicrobial Agents Elsevier Science Bv, Amsterdam., 50(3), 461-466. https://doi.org/10.1016/j.ijantimicag.2017.06.002
Srbljanović J, Štajner T, Konstantinović JM, Terzić-Jovanović N, Uzelac A, Bobić B, Šolaja BA, Đurković-Đaković O. Examination of the antimalarial potential of experimental aminoquinolines: poor in vitro effect does not preclude in vivo efficacy. in International Journal of Antimicrobial Agents. 2017;50(3):461-466. doi:10.1016/j.ijantimicag.2017.06.002 .
Srbljanović, Jelena, Štajner, Tijana, Konstantinović, Jelena M., Terzić-Jovanović, Nataša, Uzelac, Aleksandra, Bobić, Branko, Šolaja, Bogdan A., Đurković-Đaković, Olgica, "Examination of the antimalarial potential of experimental aminoquinolines: poor in vitro effect does not preclude in vivo efficacy" in International Journal of Antimicrobial Agents, 50, no. 3 (2017):461-466, https://doi.org/10.1016/j.ijantimicag.2017.06.002 . .