Article (Scientific journals)
Synthesis And Antimicrobial And Toxicological Studies Of Amino-Acid And Peptide Derivatives Of Kanamycin-A And Netilmicin
Kotretsou, S.; Mingeot-Leclercq, Marie-Paule; Constantinoukokotou, V. et al.
1995In Journal of Medicinal Chemistry, 38 (23), p. 4710-4719
Peer Reviewed verified by ORBi
 

Files


Full Text
125-cv.pdf
Publisher postprint (2.49 MB)
Request a copy

All documents in ORBi are protected by a user license.

Send to



Details



Abstract :
[en] Amino acid and peptide derivatives of aminoglycosides have been obtained by substitution of the 1-N or 6'-N amino functions of kanamycin A and netilmicin via the temporary complexation of vicinal and nonvicinal amino and hydroxy functions by copper ion [1-N kanamycin A derivatives: L-Ala (6a), D-Ala (6b), Gly (6c), L-Asp (6d), L-Ala-L-Ala (6e). 6'-N kanamycin A derivatives: L-Ala (3a), D-Ala (3b), Gly (3c), L-Ala-L-Ala (3e), L-Leu (3f). 6'-N netilmicin derivatives: L-Ala (9a), D-Ala (9b), Gly (9c), L-Asp (9d), L-Ala-L-Ala (9e)]. Characterization was made by FAB-MS, IR, 1H-NMR, and 13C-NMR. All derivatives were essentially inactive. The nephrotoxic potential of the derivatives obtained in sufficient quantities (3b,e and 9a-e) was assessed by measuring their inhibitory potential toward the activity of lysosomal phospholipase A1 acting on phosphatidylcholine embedded in negatively-charged membranes. One compound, 6'-N-L-Ala-netilmicin (9a), showed a 2-fold decrease of inhibitory potency compared to its parent drug. A conformational analysis revealed that it adopts two equally probable conformations and orientations when interacting with phosphatidylinositol. The first in which the drug lies parallel to the hydrophobic-hydrophilic interface, is similar to that of netilmicin. The second, in which the drug inserts itself in the bilayer across the hydrophilic/hydrophobic interface, is similar to that described for streptomycin, an almost non-nephrotoxic aminoglycoside.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Kotretsou, S.
Mingeot-Leclercq, Marie-Paule
Constantinoukokotou, V.
Brasseur, Robert ;  Université de Liège - ULiège > Gembloux Agro-Bio Tech
Georgiadis, Mp.
Tulkens, Pm.
Language :
English
Title :
Synthesis And Antimicrobial And Toxicological Studies Of Amino-Acid And Peptide Derivatives Of Kanamycin-A And Netilmicin
Publication date :
1995
Journal title :
Journal of Medicinal Chemistry
ISSN :
0022-2623
eISSN :
1520-4804
Publisher :
American Chemical Society, Washington, United States - District of Columbia
Volume :
38
Issue :
23
Pages :
4710-4719
4710-9
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 28 June 2010

Statistics


Number of views
42 (5 by ULiège)
Number of downloads
3 (2 by ULiège)

Scopus citations®
 
27
Scopus citations®
without self-citations
19
OpenCitations
 
24

Bibliography


Similar publications



Contact ORBi