Glycolipids and benzylammonium lipids as novel antisepsis agents: synthesis and biological characterization.
New glycolipids and a benzylammonium lipid were rationally designed by varying the chemical structure of a D-glucose-derived hit compound active as lipid A antagonist. We report the synthesis of these compounds, their in vitro activity as lipid A antagonists on HEK cells, and the capacity to inhibit LPS-induced septic shock in vivo. The lack of toxicity and the good in vivo activity suggest the use of some compounds of the panel as hits for antisepsis drug development.
Piazza
Matteo
M
Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza della Scienza 2, 20126 Milano, Italy.
Rossini
Clara
C
Della Fiorentina
Silvia
S
Pozzi
Chiara
C
Comelli
Francesca
F
Bettoni
Isabella
I
Fusi
Paola
P
Costa
Barbara
B
Peri
Francesco
F
D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D050339:Benzylammonium Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D002460:Cell Line; D015195:Drug Design; D006017:Glycolipids / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D008050:Lipid A / Q000037:antagonists & inhibitors; D008055:Lipids / Q000138:chemical synthesis* / Q000494:pharmacology; D018805:Sepsis / Q000188:drug therapy*; D012772:Shock, Septic / Q000188:drug therapy; D013329:Structure-Activity Relationship
D000890:Anti-Infective Agents; D050339:Benzylammonium Compounds; D006017:Glycolipids; D008050:Lipid A; D008055:Lipids