Novel Aminoquinoline Derivatives Significantly Reduce Parasite Load in Leishmania infantum Infected Mice

Konstantinović, Jelena M.; Videnović, Milica; Orsini, Stefania; Bogojević, Katarina; D'Alessandro, Sarah; Scaccabarozzi, Diletta; Terzić-Jovanović, Nataša; Gradoni, Luigi; Basilico, Nicoletta; Šolaja, Bogdan

doi:10.1021/acsmedchemlett.8b00053

2018

ACC_2018_acsmedchemlett.8b00053.pdf (337.6Kb)

Authors

Konstantinović, Jelena M.

Videnović, Milica

Orsini, Stefania
Bogojević, Katarina

D'Alessandro, Sarah
Scaccabarozzi, Diletta
Terzić-Jovanović, Nataša

Gradoni, Luigi
Basilico, Nicoletta
Šolaja, Bogdan

Article (Accepted Version)

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Abstract

In this Letter, a detailed analysis of 30 4-aminoquinoline-based compounds with regard to their potential as antileishmanial drugs has been carried out. Ten compounds demonstrated IC50 LT 1 mu M against promastigote stages of L. infantum and L. tropica, and five compounds showed IC50 LT 1 mu M against intramacrophage L. infantum amastigotes. Two compounds showed dose-dependent enhancement of NO and ROS production by bone marrow-derived macrophages and remarkable reduction of parasite load in vivo, with advantage of being short-term and orally active. To the best of our knowledge, this is the first example of 4-amino-7-chloroquinoline derivatives active in Leishmania infantum infected mice.

Keywords:

Leishmania infantum / promastigote / amastigote / mice model / aminoquinoline

Source:
Acs Medicinal Chemistry Letters, 2018, 9, 7, 629-634

Publisher:

American Chemical Society (ACS)

Funding / projects:

The synthesis of aminoquinoline-based antimalarials and botulinum neurotoxin A inhibitors (RS-172008)
Ministero dellIstruzione, dellUniversita e della Ricerca (PRIN) Project [20154JRJPP_004]
Serbian Academy of Sciences and Arts, Executive Programme of Scientific and Technological Cooperation between the Italian Republic and the Republic of Serbia

Note:

This is the peer-reviewed version of the following article: Konstantinović, J.; Videnović, M.; Orsini, S.; Bogojević, K.; D’Alessandro, S.; Scaccabarozzi, D.; Terzić Jovanović, N.; Gradoni, L.; Basilico, N.; Šolaja, B. A. Novel Aminoquinoline Derivatives Significantly Reduce Parasite Load in Leishmania Infantum Infected Mice. ACS Medicinal Chemistry Letters 2018, 9 (7), 629–634. https://doi.org/10.1021/acsmedchemlett.8b00053
The published version: http://cer.ihtm.bg.ac.rs/handle/123456789/2428

DOI: 10.1021/acsmedchemlett.8b00053

ISSN: 1948-5875

PubMed: 30034591

WoS: 000442964000011

Scopus: 2-s2.0-85046787760

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	6

TY  - JOUR
AU  - Konstantinović, Jelena M.
AU  - Videnović, Milica
AU  - Orsini, Stefania
AU  - Bogojević, Katarina
AU  - D'Alessandro, Sarah
AU  - Scaccabarozzi, Diletta
AU  - Terzić-Jovanović, Nataša
AU  - Gradoni, Luigi
AU  - Basilico, Nicoletta
AU  - Šolaja, Bogdan
PY  - 2018
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/3626
AB  - In this Letter, a detailed analysis of 30 4-aminoquinoline-based compounds with regard to their potential as antileishmanial drugs has been carried out. Ten compounds demonstrated IC50  LT  1 mu M against promastigote stages of L. infantum and L. tropica, and five compounds showed IC50  LT  1 mu M against intramacrophage L. infantum amastigotes. Two compounds showed dose-dependent enhancement of NO and ROS production by bone marrow-derived macrophages and remarkable reduction of parasite load in vivo, with advantage of being short-term and orally active. To the best of our knowledge, this is the first example of 4-amino-7-chloroquinoline derivatives active in Leishmania infantum infected mice.
PB  - American Chemical Society (ACS)
T2  - Acs Medicinal Chemistry Letters
T1  - Novel Aminoquinoline Derivatives Significantly Reduce Parasite Load in Leishmania infantum Infected Mice
VL  - 9
IS  - 7
SP  - 629
EP  - 634
DO  - 10.1021/acsmedchemlett.8b00053
ER  -

@article{
author = "Konstantinović, Jelena M. and Videnović, Milica and Orsini, Stefania and Bogojević, Katarina and D'Alessandro, Sarah and Scaccabarozzi, Diletta and Terzić-Jovanović, Nataša and Gradoni, Luigi and Basilico, Nicoletta and Šolaja, Bogdan",
year = "2018",
abstract = "In this Letter, a detailed analysis of 30 4-aminoquinoline-based compounds with regard to their potential as antileishmanial drugs has been carried out. Ten compounds demonstrated IC50  LT  1 mu M against promastigote stages of L. infantum and L. tropica, and five compounds showed IC50  LT  1 mu M against intramacrophage L. infantum amastigotes. Two compounds showed dose-dependent enhancement of NO and ROS production by bone marrow-derived macrophages and remarkable reduction of parasite load in vivo, with advantage of being short-term and orally active. To the best of our knowledge, this is the first example of 4-amino-7-chloroquinoline derivatives active in Leishmania infantum infected mice.",
publisher = "American Chemical Society (ACS)",
journal = "Acs Medicinal Chemistry Letters",
title = "Novel Aminoquinoline Derivatives Significantly Reduce Parasite Load in Leishmania infantum Infected Mice",
volume = "9",
number = "7",
pages = "629-634",
doi = "10.1021/acsmedchemlett.8b00053"
}

Konstantinović, J. M., Videnović, M., Orsini, S., Bogojević, K., D'Alessandro, S., Scaccabarozzi, D., Terzić-Jovanović, N., Gradoni, L., Basilico, N.,& Šolaja, B.. (2018). Novel Aminoquinoline Derivatives Significantly Reduce Parasite Load in Leishmania infantum Infected Mice. in Acs Medicinal Chemistry Letters
American Chemical Society (ACS)., 9(7), 629-634.
https://doi.org/10.1021/acsmedchemlett.8b00053

Konstantinović JM, Videnović M, Orsini S, Bogojević K, D'Alessandro S, Scaccabarozzi D, Terzić-Jovanović N, Gradoni L, Basilico N, Šolaja B. Novel Aminoquinoline Derivatives Significantly Reduce Parasite Load in Leishmania infantum Infected Mice. in Acs Medicinal Chemistry Letters. 2018;9(7):629-634.
doi:10.1021/acsmedchemlett.8b00053 .

Konstantinović, Jelena M., Videnović, Milica, Orsini, Stefania, Bogojević, Katarina, D'Alessandro, Sarah, Scaccabarozzi, Diletta, Terzić-Jovanović, Nataša, Gradoni, Luigi, Basilico, Nicoletta, Šolaja, Bogdan, "Novel Aminoquinoline Derivatives Significantly Reduce Parasite Load in Leishmania infantum Infected Mice" in Acs Medicinal Chemistry Letters, 9, no. 7 (2018):629-634,
https://doi.org/10.1021/acsmedchemlett.8b00053 . .