Enhancement of Benzothiazoles as Pteridine Reductase-1 Inhibitors for the Treatment of Trypanosomatidic Infections.
Animals
Antiprotozoal Agents
/ chemistry
Benzothiazoles
/ chemistry
Binding Sites
Catalytic Domain
Crystallography, X-Ray
Drug Design
Enzyme Inhibitors
/ chemistry
Half-Life
Leishmania major
/ drug effects
Mice
Mice, Inbred BALB C
Molecular Docking Simulation
Oxidoreductases
/ antagonists & inhibitors
Protozoan Proteins
/ antagonists & inhibitors
Structure-Activity Relationship
Trypanosoma brucei brucei
/ drug effects
Trypanosomiasis
/ drug therapy
Journal
Journal of medicinal chemistry
ISSN: 1520-4804
Titre abrégé: J Med Chem
Pays: United States
ID NLM: 9716531
Informations de publication
Date de publication:
25 04 2019
25 04 2019
Historique:
pubmed:
26
3
2019
medline:
9
6
2020
entrez:
26
3
2019
Statut:
ppublish
Résumé
2-Amino-benzo[ d]thiazole was identified as a new scaffold for the development of improved pteridine reductase-1 (PTR1) inhibitors and anti-trypanosomatidic agents. Molecular docking and crystallography guided the design and synthesis of 42 new benzothiazoles. The compounds were assessed for Trypanosoma brucei and Leishmania major PTR1 inhibition and in vitro activity against T. brucei and amastigote Leishmania infantum. We identified several 2-amino-benzo[ d]thiazoles with improved enzymatic activity ( TbPTR1 IC
Identifiants
pubmed: 30908048
doi: 10.1021/acs.jmedchem.8b02021
doi:
Substances chimiques
Antiprotozoal Agents
0
Benzothiazoles
0
Enzyme Inhibitors
0
Protozoan Proteins
0
Oxidoreductases
EC 1.-
pteridine reductase
EC 1.1.1.33
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM