Antibiotic activities and affinities for bacterial cell wall analogue of N-demethylvancomycin and its derivatives.
N-Demethylvancomycin, which has been clinically used in China, is one member of vancomycin group (glycopeptide) antibiotics. It differs from vancomycin only in that methyl group on the amino group of the N-terminal residue of vancomycin has been replaced by H. By reductive alkylation of N-demethylvancomycin, we synthesized N-alkyl and N,N'-dialkyl N-demethylvancomycins, which closely correlated with vancomycin in structure. The association constants of the complexes of N-demethylvancomycin and its analogues with di-N-Ac-L-Lys-D-Ala-D-Ala and the antibiotic activity against Staphylococcus aureus of the glycopeptides were determined. Results showed that N-demethylvancomycin has higher affinity for bacterial cell wall analogue di-N-Ac-L-Lys-D-Ala-D-Ala and more potent antibiotic activity against Staphylococcus aureus than vancomycin. Both N-alkylation and N,N'-dialkylation of N-demethylvancomycin reduced the affinity and antibiotic activity. The longer the alkyl groups, the less potent antibiotic activities and lower affinities have the glycopeptides. The antibiotic activities against Staphylococcus aureus of N-demethylvancomycin and its analogues roughly parallel their affinities for di-N-Ac-L-Lys-D-Ala-D-Ala.
Yan
H
H
Institute of Polymer Chemistry, The State Key Laboratory of Functional Polymer Materials for Adsorption and Separation, Nankai University, Tianjin, People's R. China.
Qi
D
D
Cheng
X
X
Song
Z
Z
Li
W
W
He
B
B
D000478:Alkylation; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D002473:Cell Wall / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D013211:Staphylococcus aureus / Q000187:drug effects*; D013329:Structure-Activity Relationship; D014640:Vancomycin / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D014640:Vancomycin; C041572:N-demethylvancomycin