Structure-activity relationship studies on 3,5-dinitrophenyl tetrazoles as antitubercular agents.
Eur J Med Chem
; 130: 419-432, 2017 Apr 21.
Article
in En
| MEDLINE
| ID: mdl-28279848
ABSTRACT
In this study, we described the structure-activity relationships of substituted 3,5-dinitrophenyl tetrazoles as potent antitubercular agents. These simple and readily accessible compounds possessed high in vitro antimycobacterial activities against Mycobacterium tuberculosis, including clinically isolated multidrug (MDR) and extensively drug-resistant (XDR) strains, with submicromolar minimum inhibitory concentrations (MICs). The most promising compounds showed low in vitro cytotoxicity and negligible antibacterial and antifungal activities, highlighting their highly selective antimycobacterial effects. 2-Substituted 5-(3,5-dinitrophenyl)-2H-tetrazole regioisomers, which are the dominant products of 5-(3,5-dinitrophenyl)-1H-tetrazole alkylation, showed better properties with respect to antimycobacterial activity and cytotoxicity than their 1-substituted counterparts. The 2-substituent of 5-(3,5-dinitrophenyl)-2H-tetrazole can be easily modified and can thus be used for the structure optimization of these promising antitubercular agents. The introduction of a tetrazole-5-thioalkyl moiety at position 2 of the tetrazole further increased the antimycobacterial activity. These compounds showed outstanding in vitro activity against M. tuberculosis (MIC values as low as 0.03 µM) and high activity against non-tuberculous mycobacterial strains.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Tetrazoles
/
Antitubercular Agents
Limits:
Humans
Language:
En
Journal:
Eur J Med Chem
Year:
2017
Document type:
Article
Affiliation country:
Czech Republic
Publication country:
FR
/
FRANCE
/
FRANCIA
/
FRANÇA