Identification of Novel Inhibitors of Leishmania donovani γ-Glutamylcysteine Synthetase Using Structure-Based Virtual Screening, Docking, Molecular Dynamics Simulation, and in Vitro Studies.
J Chem Inf Model
; 57(4): 815-825, 2017 04 24.
Article
in En
| MEDLINE
| ID: mdl-28322559
ABSTRACT
Trypansomatids maintain their redox balance by the trypanothione-based redox system, enzymes of which exhibit differences from mammalian homologues. γ-Glutamylcysteine synthetase (Gcs) is an essential enzyme in this pathway that performs the first and rate-limiting step. l-Buthionine-(S,R)-sulfoximine (BSO), a specific inhibitor of Gcs, induces toxicity in hosts infected with Trypanosoma brucei, underlining the need for novel Gcs inhibitors. The present study reports identification of Leishmania donovani Gcs (LdGcs) inhibitors using computational approaches and their experimental validation. Analysis of inhibitor-LdGcs complexes shows modifications that could result in increased efficacy of these compounds.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Leishmania donovani
/
Dipeptides
/
Enzyme Inhibitors
/
Molecular Dynamics Simulation
Type of study:
Diagnostic_studies
/
Screening_studies
Limits:
Humans
Language:
En
Journal:
J Chem Inf Model
Journal subject:
INFORMATICA MEDICA
/
QUIMICA
Year:
2017
Document type:
Article
Affiliation country:
India