Structure-Function Studies on IMD-0354 Identifies Highly Active Colistin Adjuvants.
ChemMedChem
; 15(2): 210-218, 2020 01 17.
Article
in En
| MEDLINE
| ID: mdl-31756025
ABSTRACT
Infections caused by multidrug-resistant (MDR) bacteria, particularly Gram-negative bacteria, are an escalating global health threat. Often clinicians are forced to administer the last-resort antibiotic colistin; however, colistin resistance is becoming increasingly prevalent, giving rise to the potential for a situation in which there are no treatment options for MDR Gram-negative infections. The development of adjuvants that circumvent bacterial resistance mechanisms is a promising orthogonal approach to the development of new antibiotics. We recently disclosed that the known IKK-ß inhibitor IMD-0354 potently suppresses colistin resistance in several Gram-negative strains. In this study, we explore the structure-activity relationship (SAR) between the IMD-0354 scaffold and colistin resistance suppression, and identify several compounds with more potent activity than the parent against highly colistin-resistant strains of Acinetobacter baumannii and Klebsiella pneumoniae.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Benzamides
/
Adjuvants, Pharmaceutic
/
Acinetobacter baumannii
/
Klebsiella pneumoniae
/
Anti-Bacterial Agents
Limits:
Humans
Language:
En
Journal:
ChemMedChem
Journal subject:
FARMACOLOGIA
/
QUIMICA
Year:
2020
Document type:
Article
Affiliation country: