Novel nitroimidazole derivatives evaluated for their trypanocidal, cytotoxic, and genotoxic activities.
Animals
Antiprotozoal Agents
/ chemical synthesis
Cell Proliferation
/ drug effects
Cell Survival
/ drug effects
Cells, Cultured
Chlorocebus aethiops
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Hep G2 Cells
Humans
Mice
Microbial Sensitivity Tests
Models, Molecular
Molecular Structure
Nitroimidazoles
/ chemical synthesis
Nitroreductases
/ antagonists & inhibitors
RAW 264.7 Cells
Salmonella enterica
/ drug effects
Structure-Activity Relationship
Trypanocidal Agents
/ chemical synthesis
Trypanosoma cruzi
/ drug effects
Chagas disease
Genotoxic activity
Molecular modeling
Nitroimidazoles
Trypanosoma cruzi
Journal
European journal of medicinal chemistry
ISSN: 1768-3254
Titre abrégé: Eur J Med Chem
Pays: France
ID NLM: 0420510
Informations de publication
Date de publication:
15 Jan 2020
15 Jan 2020
Historique:
received:
14
08
2019
revised:
12
11
2019
accepted:
13
11
2019
pubmed:
4
12
2019
medline:
19
2
2020
entrez:
3
12
2019
Statut:
ppublish
Résumé
The current treatment of Chagas disease is based on the use of two drugs, nifurtimox (Nfx) and benznidazole (Bnz), both of which present limited efficacy in the chronic stage of the disease and toxic side effects. Thus, the discovery of novel compounds is urgently required. Herein, we report the successful synthesis of 4-nitroimidazole analogs of Bnz via nucleophilic aromatic substitution or cycloaddition reactions. The analogs were biologically evaluated, and compound 4 (4-cyclopropyl-1-(1-methyl-4-nitro-1H-imidazole-5-yl)-1H-1,2,3-triazole) was identified as the most potent against both the trypomastigote (IC
Identifiants
pubmed: 31787363
pii: S0223-5234(19)31039-6
doi: 10.1016/j.ejmech.2019.111887
pii:
doi:
Substances chimiques
Antiprotozoal Agents
0
Nitroimidazoles
0
Trypanocidal Agents
0
Nitroreductases
EC 1.7.-
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
111887Informations de copyright
Copyright © 2019 Elsevier Masson SAS. All rights reserved.