HAL will be down for maintenance from Friday, June 10 at 4pm through Monday, June 13 at 9am. More information
Skip to Main content Skip to Navigation
Journal articles

Antileishmanial pharmacomodulation in 8-nitroquinolin-2(1H)-one series

Charline Kieffer 1 Anita Cohen 2 Pierre Verhaeghe 3 Lucie Paloque 3 Sébastien Hutter 2 Caroline Castera-Ducros 1 Michèle Laget 2 Sylvain Rault 4, 5 Alexis Valentin 6 Pascal Rathelot 1 Nadine Azas 2 Patrice Vanelle 1
1 ICR - Institut de Chimie Radicalaire
2 IP-TPT - Infections Parasitaires : Transmission, Physiopathologie et Thérapeutiques
3 LCC - Laboratoire de chimie de coordination
4 CERMN - Centre d'Etudes et de Recherche sur le Médicament de Normandie
5 NU - Normandie Université
6 PHARMA-DEV - Pharmacochimie et Biologie pour le Développement
Abstract : An antileishmanial pharmacomodulation at position 4 of 8-nitroquinolin-2(1H)-one was conducted by using the Sonogashira and Suzuki-Miyaura coupling reactions. A series of 25 derivatives was tested in vitro on the promastigote stage of Leishmania donovani along with an in vitro cytotoxicity evaluation on the human HepG2 cell line. Only the derivatives bearing a phenyl moiety at position 4 of the quinoline ring displayed interesting biologic profile, when the phenyl moiety was substituted at the para position by a Br or Cl atom, or by a CF3 group. Among them, molecules 17 and 19 were the most selective and were then tested in vitro on the intracellular amastigote stage of both L. donovani and Leishmania infantum, in parallel with complementary in vitro cytotoxicity assays on the macrophage cell lines THP-1 and J774A.1. Molecule 19 showed no activity on the amastigote stages of the parasites and some cytotoxicity on the J774A.1 cell line while molecule 17, less cytotoxic than 19, showed anti-amastigote activity in L. infantum, being 3 times less active than miltefosine but more active and selective than pentamidine. Nevertheless, hit-molecule 17 did not appear as selective as the parent compound. (C) 2015 Elsevier Ltd. All rights reserved.
Document type :
Journal articles
Complete list of metadata
https://hal-amu.archives-ouvertes.fr/hal-01460646
Contributor : Didier Gigmes Connect in order to contact the contributor
Submitted on : Tuesday, February 7, 2017 - 5:36:32 PM
Last modification on : Thursday, April 7, 2022 - 9:32:02 AM

Identifiers

Collections

UNIV-AMU | CNRS | SSA | INC-CNRS | COMUE-NORMANDIE | UNICAEN | CERMN | LCC | UNIV-TLSE3 | PHARMA-DEV | IRD

Citation

Charline Kieffer, Anita Cohen, Pierre Verhaeghe, Lucie Paloque, Sébastien Hutter, et al.. Antileishmanial pharmacomodulation in 8-nitroquinolin-2(1H)-one series. Bioorganic and Medicinal Chemistry, Elsevier, 2015, 23 (10), pp.2377-2386. ⟨10.1016/j.bmc.2015.03.064⟩. ⟨hal-01460646⟩

Export

BibTeX TEI DC DCterms EndNote Datacite

Share

Metrics

Record views

130