Reinvestigating Old Pharmacophores: Are 4-Aminoquinolines and Tetraoxanes Potential Two-Stage Antimalarials?
Само за регистроване кориснике
2016
Аутори
Terzić-Jovanović, NatašaKonstantinović, Jelena M.
Tot, Mikloš
Burojević, Jovana
Đurković-Đaković, Olgica
Srbljanović, Jelena
Štajner, Tijana
Verbić, Tatjana
Zlatović, Mario
Machado, Marta
Albuquerque, Ines S.
Prudencio, Miguel
Sciotii, Richard J.
Pečić, Stevan
D'Alessandro, Sarah
Taramelli, Donatella
Šolaja, Bogdan A.
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
The syntheses and antiplasmodial activities of various substituted aminoquinolines coupled to an adamantane carrier are described. The compounds exhibited pronounced in vitro and in vivo activity against Plasmodium berghei in the Thompson test. Tethering a fluorine atom to the aminoquinoline C(3) position afforded fluoroaminoquinolines that act as intrahepatocytic parasite inhibitors, with compound 25 having an IC50 = 0.31 mu M and reducing the liver load in mice by up to 92% at 80 mg/kg dose. Screening our peroxides as inhibitors of liver stage infection revealed that the tetraoxane pharmacophore itself is also an excellent liver stage P. berghei inhibitor (78: IC50 = 0.33 mu M). Up to 91% reduction of the parasite liver load in mice was achieved at 100 mg/kg. Examination of tetraoxane 78 against the transgenic 3D7 strain expressing luciferase under a gametocyte-specific promoter revealed its activity against stage IV-V Plasmodium falciparum gametocytes (IC50 = 1.16 +/- 0.37 mu M). To... the best of our knowledge, compounds 25 and 78 are the first examples of either an 4-aminoquinoline or a tetraoxane liver stage inhibitors.
Извор:
Journal of Medicinal Chemistry, 2016, 59, 1, 264-281Издавач:
- Amer Chemical Soc, Washington
Финансирање / пројекти:
- Синтеза аминохинолина и њихових деривата као антималарика и инхибитора ботулинум неуротоксина А (RS-MESTD-Basic Research (BR or ON)-172008)
- Контрола инфекција апикомплексним патогенима: од нових места деловања лека до предикције (RS-MESTD-Integrated and Interdisciplinary Research (IIR or III)-41019)
- Bill & Melinda Gates Foundation [OPP1040394]
- Serbian Academy of Sciences and Arts
- Fundacao para a Ciencia e Tecnologia, Portugal [PTDC/SAUMIC/117060/2010]
Напомена:
- Supplementary material: http://cherry.chem.bg.ac.rs/handle/123456789/3606
DOI: 10.1021/acs.jmedchem.5b01374
ISSN: 0022-2623
PubMed: 26640981
WoS: 000368564400019
Scopus: 2-s2.0-84955243433
Колекције
Институција/група
Hemijski fakultet / Faculty of ChemistryTY - JOUR AU - Terzić-Jovanović, Nataša AU - Konstantinović, Jelena M. AU - Tot, Mikloš AU - Burojević, Jovana AU - Đurković-Đaković, Olgica AU - Srbljanović, Jelena AU - Štajner, Tijana AU - Verbić, Tatjana AU - Zlatović, Mario AU - Machado, Marta AU - Albuquerque, Ines S. AU - Prudencio, Miguel AU - Sciotii, Richard J. AU - Pečić, Stevan AU - D'Alessandro, Sarah AU - Taramelli, Donatella AU - Šolaja, Bogdan A. PY - 2016 UR - https://cherry.chem.bg.ac.rs/handle/123456789/2036 AB - The syntheses and antiplasmodial activities of various substituted aminoquinolines coupled to an adamantane carrier are described. The compounds exhibited pronounced in vitro and in vivo activity against Plasmodium berghei in the Thompson test. Tethering a fluorine atom to the aminoquinoline C(3) position afforded fluoroaminoquinolines that act as intrahepatocytic parasite inhibitors, with compound 25 having an IC50 = 0.31 mu M and reducing the liver load in mice by up to 92% at 80 mg/kg dose. Screening our peroxides as inhibitors of liver stage infection revealed that the tetraoxane pharmacophore itself is also an excellent liver stage P. berghei inhibitor (78: IC50 = 0.33 mu M). Up to 91% reduction of the parasite liver load in mice was achieved at 100 mg/kg. Examination of tetraoxane 78 against the transgenic 3D7 strain expressing luciferase under a gametocyte-specific promoter revealed its activity against stage IV-V Plasmodium falciparum gametocytes (IC50 = 1.16 +/- 0.37 mu M). To the best of our knowledge, compounds 25 and 78 are the first examples of either an 4-aminoquinoline or a tetraoxane liver stage inhibitors. PB - Amer Chemical Soc, Washington T2 - Journal of Medicinal Chemistry T1 - Reinvestigating Old Pharmacophores: Are 4-Aminoquinolines and Tetraoxanes Potential Two-Stage Antimalarials? VL - 59 IS - 1 SP - 264 EP - 281 DO - 10.1021/acs.jmedchem.5b01374 ER -
@article{ author = "Terzić-Jovanović, Nataša and Konstantinović, Jelena M. and Tot, Mikloš and Burojević, Jovana and Đurković-Đaković, Olgica and Srbljanović, Jelena and Štajner, Tijana and Verbić, Tatjana and Zlatović, Mario and Machado, Marta and Albuquerque, Ines S. and Prudencio, Miguel and Sciotii, Richard J. and Pečić, Stevan and D'Alessandro, Sarah and Taramelli, Donatella and Šolaja, Bogdan A.", year = "2016", abstract = "The syntheses and antiplasmodial activities of various substituted aminoquinolines coupled to an adamantane carrier are described. The compounds exhibited pronounced in vitro and in vivo activity against Plasmodium berghei in the Thompson test. Tethering a fluorine atom to the aminoquinoline C(3) position afforded fluoroaminoquinolines that act as intrahepatocytic parasite inhibitors, with compound 25 having an IC50 = 0.31 mu M and reducing the liver load in mice by up to 92% at 80 mg/kg dose. Screening our peroxides as inhibitors of liver stage infection revealed that the tetraoxane pharmacophore itself is also an excellent liver stage P. berghei inhibitor (78: IC50 = 0.33 mu M). Up to 91% reduction of the parasite liver load in mice was achieved at 100 mg/kg. Examination of tetraoxane 78 against the transgenic 3D7 strain expressing luciferase under a gametocyte-specific promoter revealed its activity against stage IV-V Plasmodium falciparum gametocytes (IC50 = 1.16 +/- 0.37 mu M). To the best of our knowledge, compounds 25 and 78 are the first examples of either an 4-aminoquinoline or a tetraoxane liver stage inhibitors.", publisher = "Amer Chemical Soc, Washington", journal = "Journal of Medicinal Chemistry", title = "Reinvestigating Old Pharmacophores: Are 4-Aminoquinolines and Tetraoxanes Potential Two-Stage Antimalarials?", volume = "59", number = "1", pages = "264-281", doi = "10.1021/acs.jmedchem.5b01374" }
Terzić-Jovanović, N., Konstantinović, J. M., Tot, M., Burojević, J., Đurković-Đaković, O., Srbljanović, J., Štajner, T., Verbić, T., Zlatović, M., Machado, M., Albuquerque, I. S., Prudencio, M., Sciotii, R. J., Pečić, S., D'Alessandro, S., Taramelli, D.,& Šolaja, B. A.. (2016). Reinvestigating Old Pharmacophores: Are 4-Aminoquinolines and Tetraoxanes Potential Two-Stage Antimalarials?. in Journal of Medicinal Chemistry Amer Chemical Soc, Washington., 59(1), 264-281. https://doi.org/10.1021/acs.jmedchem.5b01374
Terzić-Jovanović N, Konstantinović JM, Tot M, Burojević J, Đurković-Đaković O, Srbljanović J, Štajner T, Verbić T, Zlatović M, Machado M, Albuquerque IS, Prudencio M, Sciotii RJ, Pečić S, D'Alessandro S, Taramelli D, Šolaja BA. Reinvestigating Old Pharmacophores: Are 4-Aminoquinolines and Tetraoxanes Potential Two-Stage Antimalarials?. in Journal of Medicinal Chemistry. 2016;59(1):264-281. doi:10.1021/acs.jmedchem.5b01374 .
Terzić-Jovanović, Nataša, Konstantinović, Jelena M., Tot, Mikloš, Burojević, Jovana, Đurković-Đaković, Olgica, Srbljanović, Jelena, Štajner, Tijana, Verbić, Tatjana, Zlatović, Mario, Machado, Marta, Albuquerque, Ines S., Prudencio, Miguel, Sciotii, Richard J., Pečić, Stevan, D'Alessandro, Sarah, Taramelli, Donatella, Šolaja, Bogdan A., "Reinvestigating Old Pharmacophores: Are 4-Aminoquinolines and Tetraoxanes Potential Two-Stage Antimalarials?" in Journal of Medicinal Chemistry, 59, no. 1 (2016):264-281, https://doi.org/10.1021/acs.jmedchem.5b01374 . .