Identification and structure-activity relationships for a series of N, N-disubstituted 2-aminobenzothiazoles as potent inhibitors of S. aureus.
Bioorg Med Chem Lett
; 89: 129301, 2023 06 01.
Article
in En
| MEDLINE
| ID: mdl-37094726
ABSTRACT
An internal collection of commercial and synthetically derived small molecule compounds was screened against several drug-resistant bacterial pathogens. Compound 1, a known N, N-disubstituted 2-aminobenzothiazole, was found to be a potent inhibitor of Staphylococcus aureus and several associated clinically relevant strains of methicillin-resistant S. aureus suggesting a possible novel mechanism of inhibition. It failed to show activity in any of the Gram-negative pathogens it was tested in. Evaluation in Escherichia coli BW25113 and Pseudomonas aeruginosa PAO1, as well as in their respective hyperporinated and efflux pump-deletion mutants revealed that activity in Gram-negative bacteria is diminished because this benzothiazole scaffold is a substrate for bacterial efflux pumps. Several analogs of 1 were synthesized to generate basic structure-activity relationships for the scaffold which highlighted that the N-propyl imidazole moiety was critical for the observed antibacterial activity.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Staphylococcus aureus
/
Methicillin-Resistant Staphylococcus aureus
Type of study:
Diagnostic_studies
Language:
En
Journal:
Bioorg Med Chem Lett
Journal subject:
BIOQUIMICA
/
QUIMICA
Year:
2023
Type:
Article
Affiliation country:
United States