Synthesis of Tridecaptin-Antibiotic Conjugates with in Vivo Activity against Gram-Negative Bacteria

被引：43

作者：

Cochrane, Stephen A. ^{[1
]}

Li, Xuefeng ^{[2
]}

He, Sisi ^{[2
]}

Yu, Min ^{[2
]}

Wu, Min ^{[2
]}

Vederas, John C. ^{[1
]}

机构：

[1] Univ Alberta, Dept Chem, Edmonton, AB T6G 2G2, Canada

[2] Univ N Dakota, Sch Med & Hlth Sci, Dept Biomed Sci, Grand Forks, ND 58203 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2015年 / 58卷 / 24期

基金：

美国国家卫生研究院; 加拿大自然科学与工程研究理事会;

关键词：

A(1); DRUG; ANALOGS;

D O I：

10.1021/acs.jmedchem.5b01578

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of tridecaptin-antibiotic conjugates were synthesized and evaluated for in vitro and in vivo activity against Gram-negative bacteria. Covalently linking unacylated tridecaptin A(1) (H-TriA(1)) to rifampicin, vancomycin, and erythromycin enhanced their activity in vitro but not by the same magnitude as coadministration of the peptide and these antibiotics. The antimicrobial activities of the conjugates were retained in vivo, with the H-TriA(1)-erythromycin conjugate proving a more effective treatment of Klebseilla pneumoniae infections in mice than erythromycin alone or in combination with H-TriA(1).

引用

页码：9779 / 9785

页数：7

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