Synthesis and preliminary anti-inflammatory and anti-bacterial evaluation of some diflunisal aza-analogs.
Medchemcomm
; 9(6): 1017-1032, 2018 Jun 01.
Article
em En
| MEDLINE
| ID: mdl-30108991
ABSTRACT
Our aim was to identify new multi-target compounds endowed with both anti-inflammatory and anti-bacterial activities for treatment of human infections. Diflunisal, a nonsteroidal anti-inflammatory agent, has recently been repurposed for its anti-virulence properties against methicillin-resistant Staphylococcus aureus. Effective synthesis of some aza-analogs of the anti-inflammatory drug diflunisal was carried out following the route involving key oxazole intermediates to obtain o- and m-hydroxypyridinecarboxylic acid derivatives. The newly synthesized diflunisal aza-analogs did not exhibit cytotoxic activity up to 80 µM and some of them exhibited anti-inflammatory activities, decreasing the levels of pro-inflammatory cytokines and prostaglandins induced by bacterial lipopolysaccharide in human primary macrophages. Ten of the diflunisal aza-analogs were found to have interesting antibacterial activity, sensitizing S. aureus, Streptococcus pyogenes, Enterococcus faecium, and Pseudomonas aeruginosa to the antibacterial effects of beta-lactam antibiotics and protein synthesis inhibitors.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article