Discovery of macrozones, new antimicrobial thiosemicarbazone-based azithromycin conjugates: design, synthesis and in vitro biological evaluation.
Int J Antimicrob Agents
; 56(5): 106147, 2020 Nov.
Article
in En
| MEDLINE
| ID: mdl-32853671
ABSTRACT
Increasing bacterial resistance to existing antibiotics presents a serious threat to human health, and new antibacterial agents are desperately needed. Unfortunately, the number of newly marketed antibiotics has decreased dramatically in recent years. Withdrawal of the macrolide antibiotic telithromycin and the inability of solithromycin to gain marketing approval have prompted our efforts to search for new anti-infective macrolide compounds. Here we present the design, synthesis and biological evaluation of a novel hybrid class of azithromycin conjugates, the macrozones. Evaluation of prepared compounds against a panel of pathogenic bacteria revealed that these molecules showed excellent activities against susceptible Streptococcus pneumoniae, Streptococcus pyogenes and Enterococcus faecalis strains comparable with or better than azithromycin. Furthermore, prepared macrozones exhibited excellent activity against efflux resistant S. pneumoniae, which was 32 times better than that of azithromycin, and very good activity against an efflux resistant Staphylococcus aureus strain against which azithromycin is inactive. The results described here can serve as a good basis to guide further activities directed toward the discovery of more potent macrolide anti-infectives.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Thiosemicarbazones
/
Drug Design
/
Azithromycin
/
Anti-Bacterial Agents
Language:
En
Journal:
Int J Antimicrob Agents
Year:
2020
Document type:
Article
Affiliation country:
Croacia