TY  - JOUR
AU  - Manzano, Jose Ignacio
AU  - Konstantinović, Jelena
AU  - Scaccabarozzi, Diletta
AU  - Perea, Ana
AU  - Pavić, Aleksandar
AU  - Cavicchini, Loredana
AU  - Basilico, Nicoletta
AU  - Gamarro, Francisco
AU  - Solaja, Bogdan A.
PY  - 2019
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1198
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  lt  1 mu M. 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 France-Editions Scientifiques Medicales Elsevier, Issy-Les-Moulineaux
T2  - European Journal of Medicinal Chemistry
T1  - 4-Aminoquinoline-based compounds as antileishmanial agents that inhibit the energy metabolism of Leishmania
EP  - 40
SP  - 28
VL  - 180
DO  - 10.1016/j.ejmech.2019.07.010
ER  - 

@article{
author = "Manzano, Jose Ignacio and Konstantinović, Jelena and Scaccabarozzi, Diletta and Perea, Ana and Pavić, Aleksandar and Cavicchini, Loredana and Basilico, Nicoletta and Gamarro, Francisco and Solaja, 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  lt  1 mu M. 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 France-Editions Scientifiques Medicales Elsevier, Issy-Les-Moulineaux",
journal = "European Journal of Medicinal Chemistry",
title = "4-Aminoquinoline-based compounds as antileishmanial agents that inhibit the energy metabolism of Leishmania",
pages = "40-28",
volume = "180",
doi = "10.1016/j.ejmech.2019.07.010"
}

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

Manzano JI, Konstantinović J, Scaccabarozzi D, Perea A, Pavić A, Cavicchini L, Basilico N, Gamarro F, Solaja 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, Scaccabarozzi, Diletta, Perea, Ana, Pavić, Aleksandar, Cavicchini, Loredana, Basilico, Nicoletta, Gamarro, Francisco, Solaja, 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 . .