Novel dendrimeric lipopeptides with antifungal activity.
A series of new cationic lipopeptides containing branched, amphiphilic polar head derived from (Lys)Lys(Lys) dendron and C(8) or C(12) chain at C-end were designed, synthesized and characterized. Antimicrobial in vitro activity expressed as minimal inhibitory concentration (MIC) was evaluated against Gram-positive and Gram-negative bacteria and yeasts from the Candida genus. A significant enhancement of antimicrobial potency along with increased selectivity against Candida reference strains was detected for derivatives with the C(12) residue. Several compounds were characterized by a low hemotoxicity. The antifungal activity of branched lipopeptides is multimodal and concentration dependent. Several compounds, studied in detail, induced potassium leakage from fungal cells, caused morphological alterations of fungal cells and inhibited activity of candidal β(1,3)-glucan synthase.
Institute of Industrial Research, L. Rydygiera 8, 01-793 Warsaw, Poland.
Jolanta
J
Janiszewska
Marta
M
Sowińska
Aleksandra
A
Rajnisz
Jolanta
J
Solecka
Izabela
I
Łącka
Sławomir
S
Milewski
Zofia
Z
Urbańczyk-Lipkowska
D000935:Antifungal Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects; D002175:Candida / Q000187:drug effects* / Q000201:enzymology / Q000648:ultrastructure; D002412:Cations; D050091:Dendrimers / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D015195:Drug Design; D004912:Erythrocytes / Q000187:drug effects; D005964:Glucosyltransferases / Q000037:antagonists & inhibitors; D006801:Humans; D055666:Lipopeptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure
D000935:Antifungal Agents; D002412:Cations; D050091:Dendrimers; D055666:Lipopeptides; D005964:Glucosyltransferases; C040232:glucan synthase