Synthesis and in vitro antibacterial activity of catechol-spiramycin conjugates.
The first synthesis of siderophore conjugates of two macrolide antibiotics, spiramycin 1 and neospiramycin 2, which are unable to penetrate the outer membrane of gram-negative bacteria are described. These novel conjugates were prepared by regioselective acylation of a hydroxyl function of 1 and 2 with a dihydroxybenzoic Fe(III) complexing ligand linked via a carboxyl group containing spacer to the macrolide antibiotics. The preliminary biological evaluation of these novel conjugates under standard and iron depleted conditions has shown that their antibacterial activity was comparable to that of spiramycin 1 and neospiramycin 2.
Poras
H
H
Laboratoire de Chimie Bioorganique et Bioinorganique (CNRS, URA 1384), Université de Paris-Sud, Centre d'Orsay, France.
Kunesch
G
G
Barrière
J C
JC
Berthaud
N
N
Andremont
A
A
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D002396:Catechols / Q000138:chemical synthesis / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D015572:Spiramycin / Q000031:analogs & derivatives / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D002396:Catechols; C090280:neospiramycin; D015572:Spiramycin