Synthesis of Tridecaptin-Antibiotic Conjugates with in Vivo Activity against Gram-Negative Bacteria
Synthesis of Tridecaptin-Antibiotic Conjugates with in Vivo Activity against Gram-Negative Bacteria
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DOI：
10.1021/acs.jmedchem.5b01578
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发表时间：
2015-12-24
影响因子：
7.3
通讯作者：
Vederas, John C.
中科院分区：
文献类型：
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作者：
Cochrane, Stephen A.;Li, Xuefeng;Vederas, John C.
合成了一系列tridecaptin-抗生素缀合物，并评价了其对革兰氏阴性菌的体外和体内活性。将未酰化的tridecaptin A（1）（H-TriA（1））与利福平、万古霉素和红霉素连接的肽在体外增强了它们的活性，但与肽和这些抗生素共同给药的幅度不同。结合物的抗微生物活性在体内得以保留，H-TriA（1）-红霉素结合物证明比红霉素单独或与H-TriA（1）联合治疗小鼠肺炎克雷伯氏菌感染更有效。
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).