Impact of Pyridyl Moieties on the Inhibitory Properties of Prominent Acyclic Metal Chelators Against Metallo-ß-Lactamase-Producing Enterobacteriaceae: Investigating the Molecular Basis of Acyclic Metal Chelators' Activity.
Microb Drug Resist
; 25(3): 439-449, 2019 Apr.
Article
in En
| MEDLINE
| ID: mdl-30741600
ABSTRACT
Carbapenem-resistant Enterobacteriaceae (CREs)-mediated infections remain a huge public health concern. CREs produce enzymes such as metallo-ß-lactamases (MBLs), which inactivate ß-lactam antibiotics. Hence, developing efficient molecules capable of inhibiting these enzymes remains a way forward to overcoming this phenomenon. In this study, we demonstrate that pyridyl moieties favor the inhibitory activity of cyclic metal-chelating agents through in vitro screening, molecular modeling, and docking assays. Di-(2-picolyl) amine and tris-(2-picolyl) amine exhibited great efficacy against different types of MBLs and strong binding affinity for NDM-1, whereas 2-picolyl amine did not show activity at a concentration of 64 mg/L in combination with meropenem; it further showed the lowest binding affinity from computational molecular analysis, commensurating with the in vitro screening assays. The findings revealed that the pyridyl group plays a vital role in the inhibitory activity of the tested molecules against CREs and should be exploited as potential MBL inhibitors.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Beta-Lactamases
/
Chelating Agents
/
Enterobacteriaceae
/
Enterobacteriaceae Infections
/
Anti-Bacterial Agents
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Microb Drug Resist
Journal subject:
MICROBIOLOGIA
/
TERAPIA POR MEDICAMENTOS
Year:
2019
Document type:
Article
Affiliation country: