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

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

Research output: Contribution to journalArticle

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 < 1 μM against promastigote stages of L. infantum and L. tropica, and five compounds showed IC50 < 1 μM 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.

Original languageEnglish
Pages (from-to)629-634
Number of pages6
JournalACS Medicinal Chemistry Letters
Volume9
Issue number7
DOIs
Publication statusPublished - Jul 12 2018

Fingerprint

Aminoquinolines
Parasite Load
Leishmania infantum
Macrophages
Bone
Derivatives
Inhibitory Concentration 50
Pharmaceutical Preparations
4-aminoquinoline
Parasites

Cite this

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

Novel Aminoquinoline Derivatives Significantly Reduce Parasite Load in Leishmania infantum Infected Mice. / Konstantinović, Jelena; Videnović, Milica; Orsini, Stefania; Bogojević, Katarina; D'Alessandro, Sarah; Scaccabarozzi, Diletta; Terzić Jovanović, Nataša; Gradoni, Luigi; Basilico, Nicoletta; Šolaja, Bogdan A.

In: ACS Medicinal Chemistry Letters, Vol. 9, No. 7, 12.07.2018, p. 629-634.

Research output: Contribution to journalArticle

Konstantinović, J, Videnović, M, Orsini, S, Bogojević, K, D'Alessandro, S, Scaccabarozzi, D, Terzić Jovanović, N, Gradoni, L, Basilico, N & Šolaja, BA 2018, 'Novel Aminoquinoline Derivatives Significantly Reduce Parasite Load in Leishmania infantum Infected Mice', ACS Medicinal Chemistry Letters, vol. 9, no. 7, pp. 629-634. https://doi.org/10.1021/acsmedchemlett.8b00053
Konstantinović J, Videnović M, Orsini S, Bogojević K, D'Alessandro S, Scaccabarozzi D et al. Novel Aminoquinoline Derivatives Significantly Reduce Parasite Load in Leishmania infantum Infected Mice. ACS Medicinal Chemistry Letters. 2018 Jul 12;9(7):629-634. https://doi.org/10.1021/acsmedchemlett.8b00053
Konstantinović, Jelena ; Videnović, Milica ; Orsini, Stefania ; Bogojević, Katarina ; D'Alessandro, Sarah ; Scaccabarozzi, Diletta ; Terzić Jovanović, Nataša ; Gradoni, Luigi ; Basilico, Nicoletta ; Šolaja, Bogdan A. / Novel Aminoquinoline Derivatives Significantly Reduce Parasite Load in Leishmania infantum Infected Mice. In: ACS Medicinal Chemistry Letters. 2018 ; Vol. 9, No. 7. pp. 629-634.
@article{3d27616dd075465688a601ef7b62fd4b,
title = "Novel Aminoquinoline Derivatives Significantly Reduce Parasite Load in Leishmania infantum Infected Mice",
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 < 1 μM against promastigote stages of L. infantum and L. tropica, and five compounds showed IC50 < 1 μM 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.",
author = "Jelena Konstantinović and Milica Videnović and Stefania Orsini and Katarina Bogojević and Sarah D'Alessandro and Diletta Scaccabarozzi and {Terzić Jovanović}, Nataša and Luigi Gradoni and Nicoletta Basilico and Šolaja, {Bogdan A}",
year = "2018",
month = "7",
day = "12",
doi = "10.1021/acsmedchemlett.8b00053",
language = "English",
volume = "9",
pages = "629--634",
journal = "ACS Medicinal Chemistry Letters",
issn = "1948-5875",
publisher = "American Chemical Society",
number = "7",

}

TY - JOUR

T1 - Novel Aminoquinoline Derivatives Significantly Reduce Parasite Load in Leishmania infantum Infected Mice

AU - Konstantinović, Jelena

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 A

PY - 2018/7/12

Y1 - 2018/7/12

N2 - 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 < 1 μM against promastigote stages of L. infantum and L. tropica, and five compounds showed IC50 < 1 μM 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.

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 < 1 μM against promastigote stages of L. infantum and L. tropica, and five compounds showed IC50 < 1 μM 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.

U2 - 10.1021/acsmedchemlett.8b00053

DO - 10.1021/acsmedchemlett.8b00053

M3 - Article

C2 - 30034591

VL - 9

SP - 629

EP - 634

JO - ACS Medicinal Chemistry Letters

JF - ACS Medicinal Chemistry Letters

SN - 1948-5875

IS - 7

ER -