Structure-activity relationship studies of lipophilic teicoplanin pseudoaglycon derivatives as new anti-influenza virus agents.
Eur J Med Chem
; 157: 1017-1030, 2018 Sep 05.
Article
in En
| MEDLINE
| ID: mdl-30170320
ABSTRACT
Six series of semisynthetic lipophilic glycopeptide antibiotic derivatives were evaluated for in vitro activity against influenza A and B viruses. The new teicoplanin pseudoaglycon-derived lipoglycopeptides were prepared by coupling one or two side chains to the N-terminus of the glycopeptide core, using various conjugation methods. Three series of derivatives bearing two lipophilic groups were synthesized by attaching bis-alkylthio maleimides directly or through linkers of different lengths to the glycopeptide. Access to the fourth and fifth series of compounds was achieved by click chemistry, introducing single alkyl/aryl chains directly or through a tetraethylene glycol linker to the same position. A sixth group of semisynthetic derivatives was obtained by sulfonylation of the N-terminus. Of the 42 lipophilic teicoplanin pseudoaglycon derivatives tested, about half showed broad activity against influenza A and B viruses, with some of them having reasonable or no cytotoxicity. Minor differences in the side chain length as well as lipophilicity appeared to have significant impact on antiviral activity and cytotoxicity. Several lipoglycopeptides were also found to be active against human coronavirus.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Antiviral Agents
/
Influenza A virus
/
Influenza B virus
/
Teicoplanin
Limits:
Humans
Language:
En
Journal:
Eur J Med Chem
Year:
2018
Document type:
Article
Affiliation country:
Hungary