TY  - JOUR
AU  - Manzano, Jose Ignacio
AU  - Konstantinović, Jelena M.
AU  - Scaccabarozzi, Diletta
AU  - Perea, Ana
AU  - Pavić, Aleksandar
AU  - Cavicchini, Loredana
AU  - Basilico, Nicoletta
AU  - Gamarro, Francisco
AU  - Šolaja, Bogdan A.
PY  - 2019
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/3287
AB  - Among neglected tropical diseases, leishmaniasis is one of the most relevant with an estimated 30,000 deaths annually. Existing therapies have serious drawbacks in safety, drug resistance, field-adapted application and cost; therefore, new safer and shorter treatments are needed for this disease. Here we report on the synthesis of novel 4-amino-7-chloroquinoline-based compounds with leishmanicidal activity, together with deeper insight into the mechanism of action of our previously published hit compound 1. New derivatives showed comparable activity to 1 against both promastigote and intracellular amastigote forms of Leishmania infantum, with IC50 < 1 mM. Furthermore, we have determined that compound 1 induced a decrease of intracellular ATP levels, as well as a mitochondrial depolarization, together with an alteration of plasma membrane permeability and a significant ROS production. The inhibition of the energy metabolism of Leishmania plays an important role in the leishmanicidal mechanism of this compound. In all, these results support the consideration of compound 1 for the future development of new leishmanicidal drugs.
PB  - Elsevier
T2  - European Journal of Medicinal Chemistry
T1  - 4-Aminoquinoline-based compounds as antileishmanial agents that inhibit the energy metabolism of Leishmania
VL  - 180
SP  - 28
EP  - 40
DO  - 10.1016/j.ejmech.2019.07.010
ER  - 

@article{
author = "Manzano, Jose Ignacio and Konstantinović, Jelena M. and Scaccabarozzi, Diletta and Perea, Ana and Pavić, Aleksandar and Cavicchini, Loredana and Basilico, Nicoletta and Gamarro, Francisco and Šolaja, Bogdan A.",
year = "2019",
abstract = "Among neglected tropical diseases, leishmaniasis is one of the most relevant with an estimated 30,000 deaths annually. Existing therapies have serious drawbacks in safety, drug resistance, field-adapted application and cost; therefore, new safer and shorter treatments are needed for this disease. Here we report on the synthesis of novel 4-amino-7-chloroquinoline-based compounds with leishmanicidal activity, together with deeper insight into the mechanism of action of our previously published hit compound 1. New derivatives showed comparable activity to 1 against both promastigote and intracellular amastigote forms of Leishmania infantum, with IC50 < 1 mM. Furthermore, we have determined that compound 1 induced a decrease of intracellular ATP levels, as well as a mitochondrial depolarization, together with an alteration of plasma membrane permeability and a significant ROS production. The inhibition of the energy metabolism of Leishmania plays an important role in the leishmanicidal mechanism of this compound. In all, these results support the consideration of compound 1 for the future development of new leishmanicidal drugs.",
publisher = "Elsevier",
journal = "European Journal of Medicinal Chemistry",
title = "4-Aminoquinoline-based compounds as antileishmanial agents that inhibit the energy metabolism of Leishmania",
volume = "180",
pages = "28-40",
doi = "10.1016/j.ejmech.2019.07.010"
}

Manzano, J. I., Konstantinović, J. M., Scaccabarozzi, D., Perea, A., Pavić, A., Cavicchini, L., Basilico, N., Gamarro, F.,& Šolaja, B. A.. (2019). 4-Aminoquinoline-based compounds as antileishmanial agents that inhibit the energy metabolism of Leishmania. in European Journal of Medicinal Chemistry
Elsevier., 180, 28-40.
https://doi.org/10.1016/j.ejmech.2019.07.010

Manzano JI, Konstantinović JM, Scaccabarozzi D, Perea A, Pavić A, Cavicchini L, Basilico N, Gamarro F, Šolaja BA. 4-Aminoquinoline-based compounds as antileishmanial agents that inhibit the energy metabolism of Leishmania. in European Journal of Medicinal Chemistry. 2019;180:28-40.
doi:10.1016/j.ejmech.2019.07.010 .

Manzano, Jose Ignacio, Konstantinović, Jelena M., Scaccabarozzi, Diletta, Perea, Ana, Pavić, Aleksandar, Cavicchini, Loredana, Basilico, Nicoletta, Gamarro, Francisco, Šolaja, Bogdan A., "4-Aminoquinoline-based compounds as antileishmanial agents that inhibit the energy metabolism of Leishmania" in European Journal of Medicinal Chemistry, 180 (2019):28-40,
https://doi.org/10.1016/j.ejmech.2019.07.010 . .

TY  - DATA
AU  - Manzano, Jose Ignacio
AU  - Konstantinović, Jelena M.
AU  - Scaccabarozzi, Diletta
AU  - Perea, Ana
AU  - Pavić, Aleksandar
AU  - Cavicchini, Loredana
AU  - Basilico, Nicoletta
AU  - Gamarro, Francisco
AU  - Šolaja, Bogdan A.
PY  - 2019
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/3288
PB  - Elsevier
T2  - European Journal of Medicinal Chemistry
T1  - Supplementary material for the article: Manzano, J. I.; Konstantinović, J.; Scaccabarozzi, D.; Perea, A.; Pavić, A.; Cavicchini, L.; Basilico, N.; Gamarro, F.; Šolaja, B. A. 4-Aminoquinoline-Based Compounds as Antileishmanial Agents That Inhibit the Energy Metabolism of Leishmania. European Journal of Medicinal Chemistry 2019, 180, 28–40. https://doi.org/10.1016/j.ejmech.2019.07.010
UR  - https://hdl.handle.net/21.15107/rcub_cherry_3288
ER  - 

@misc{
author = "Manzano, Jose Ignacio and Konstantinović, Jelena M. and Scaccabarozzi, Diletta and Perea, Ana and Pavić, Aleksandar and Cavicchini, Loredana and Basilico, Nicoletta and Gamarro, Francisco and Šolaja, Bogdan A.",
year = "2019",
publisher = "Elsevier",
journal = "European Journal of Medicinal Chemistry",
title = "Supplementary material for the article: Manzano, J. I.; Konstantinović, J.; Scaccabarozzi, D.; Perea, A.; Pavić, A.; Cavicchini, L.; Basilico, N.; Gamarro, F.; Šolaja, B. A. 4-Aminoquinoline-Based Compounds as Antileishmanial Agents That Inhibit the Energy Metabolism of Leishmania. European Journal of Medicinal Chemistry 2019, 180, 28–40. https://doi.org/10.1016/j.ejmech.2019.07.010",
url = "https://hdl.handle.net/21.15107/rcub_cherry_3288"
}

Manzano, J. I., Konstantinović, J. M., Scaccabarozzi, D., Perea, A., Pavić, A., Cavicchini, L., Basilico, N., Gamarro, F.,& Šolaja, B. A.. (2019). Supplementary material for the article: Manzano, J. I.; Konstantinović, J.; Scaccabarozzi, D.; Perea, A.; Pavić, A.; Cavicchini, L.; Basilico, N.; Gamarro, F.; Šolaja, B. A. 4-Aminoquinoline-Based Compounds as Antileishmanial Agents That Inhibit the Energy Metabolism of Leishmania. European Journal of Medicinal Chemistry 2019, 180, 28–40. https://doi.org/10.1016/j.ejmech.2019.07.010. in European Journal of Medicinal Chemistry
Elsevier..
https://hdl.handle.net/21.15107/rcub_cherry_3288

Manzano JI, Konstantinović JM, Scaccabarozzi D, Perea A, Pavić A, Cavicchini L, Basilico N, Gamarro F, Šolaja BA. Supplementary material for the article: Manzano, J. I.; Konstantinović, J.; Scaccabarozzi, D.; Perea, A.; Pavić, A.; Cavicchini, L.; Basilico, N.; Gamarro, F.; Šolaja, B. A. 4-Aminoquinoline-Based Compounds as Antileishmanial Agents That Inhibit the Energy Metabolism of Leishmania. European Journal of Medicinal Chemistry 2019, 180, 28–40. https://doi.org/10.1016/j.ejmech.2019.07.010. in European Journal of Medicinal Chemistry. 2019;.
https://hdl.handle.net/21.15107/rcub_cherry_3288 .

Manzano, Jose Ignacio, Konstantinović, Jelena M., Scaccabarozzi, Diletta, Perea, Ana, Pavić, Aleksandar, Cavicchini, Loredana, Basilico, Nicoletta, Gamarro, Francisco, Šolaja, Bogdan A., "Supplementary material for the article: Manzano, J. I.; Konstantinović, J.; Scaccabarozzi, D.; Perea, A.; Pavić, A.; Cavicchini, L.; Basilico, N.; Gamarro, F.; Šolaja, B. A. 4-Aminoquinoline-Based Compounds as Antileishmanial Agents That Inhibit the Energy Metabolism of Leishmania. European Journal of Medicinal Chemistry 2019, 180, 28–40. https://doi.org/10.1016/j.ejmech.2019.07.010" in European Journal of Medicinal Chemistry (2019),
https://hdl.handle.net/21.15107/rcub_cherry_3288 .