Activity of singly and doubly modified derivatives of C20-epi-salinomycin against Staphylococcus strains
Natural polyether ionophore salinomycin ( Sal ) has been widely used in veterinary medicine as an antibiotic effective in the treatment of coccidian protozoa and Gram-positive bacteria. Moreover, chemical modification of the Sal structure has been found to be a promising strategy to generate semisyn...
Saved in:
Published in | Journal of antibiotics Vol. 75; no. 8; pp. 445 - 453 |
---|---|
Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
London
Nature Publishing Group UK
01.08.2022
Nature Publishing Group |
Subjects | |
Online Access | Get full text |
Cover
Loading…
Summary: | Natural polyether ionophore salinomycin (
Sal
) has been widely used in veterinary medicine as an antibiotic effective in the treatment of coccidian protozoa and Gram-positive bacteria. Moreover, chemical modification of the
Sal
structure has been found to be a promising strategy to generate semisynthetic analogs with biological activity profiles improved relative to those of the native compound. In this context, we synthesized and thoroughly evaluated the antibacterial potential of a library of C1/C20 singly and doubly modified derivatives of C20-epi-salinomycin, that is, analogs of
Sal
with inversed stereochemistry at the C20 position. Among the synthesized analog structures, the most promising antibacterial active agents were those obtained via regioselective
O
-acylation of C20-epi-hydroxyl, particularly esters
7
,
9
, and
11
. Such C20 singly modified compounds showed excellent inhibitory activity against planktonic staphylococci, both standard and clinical strains, and revealed potential in preventing the formation of bacterial biofilms. In combination with their non-genotoxic properties, these
Sal
derivatives represent attractive candidates for further antimicrobial drug development. |
---|---|
Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0021-8820 1881-1469 |
DOI: | 10.1038/s41429-022-00536-4 |