当前位置：
X-MOL 学术
›
J. Med. Chem.
›
论文详情
Our official English website, www.x-mol.net, welcomes your
feedback! (Note: you will need to create a separate account there.)
New Polyaminoisoprenyl Antibiotics Enhancers against Two Multidrug-Resistant Gram-Negative Bacteria from Enterobacter and Salmonella Species.
Journal of Medicinal Chemistry ( IF 6.8 ) Pub Date : 2020-08-25 , DOI: 10.1021/acs.jmedchem.0c01335 Aurélie Lieutaud 1 , Cyril Pieri 1 , Jean Michel Bolla 1 , Jean Michel Brunel 1
Journal of Medicinal Chemistry ( IF 6.8 ) Pub Date : 2020-08-25 , DOI: 10.1021/acs.jmedchem.0c01335 Aurélie Lieutaud 1 , Cyril Pieri 1 , Jean Michel Bolla 1 , Jean Michel Brunel 1
Affiliation
|
A series consisting of new polyaminoisoprenyl derivatives were prepared in moderate to good chemical yields varying from 32 to 64% according to two synthetic pathways: (1) using a titanium-reductive amination reaction affording a 50/50 mixture of cis and trans isomers and (2) a direct nucleophilic substitution leading to a stereoselective synthesis of the compounds of interest. These compounds were then successfully evaluated for their in vitro antibiotic enhancer properties against resistant Gram-negative bacteria of four antibiotics belonging to four different families. The mechanism of action against Enterobacter aerogenes of one of the most efficient of these chemosensitizing agents was precisely evaluated by using fluorescent dyes to measure outer-membrane permeability and to determine membrane depolarization. The weak cytotoxicity encountered led us to perform an in vivo experiment dealing with the treatment of mice infected with Salmonella typhimurium and affording preliminary promising results in terms of tolerance and efficiency of the polyaminoisoprenyl derivative 5r/doxycycline combination.
中文翻译：
针对两种来自肠杆菌和沙门氏菌的多重耐药革兰氏阴性细菌的新型聚氨基异戊二烯抗生素增强剂。
根据两种合成途径，制备了一系列由新的聚氨基异戊二烯衍生物组成的化合物，其化学收率在32％至64％之间，变化范围为中度至良好：（1）使用钛还原胺化反应提供50/50的顺式和反式异构体混合物，以及2）直接亲核取代，导致目标化合物的立体选择性合成。然后成功地评估了这些化合物的体外抗生素增强剂对四种不同家族的四种抗生素的革兰氏阴性细菌的抵抗力。对抗产气肠杆菌的作用机理通过使用荧光染料测量外膜通透性并确定膜去极化，可以精确评估其中一种最有效的化学增敏剂。遇到的弱细胞毒性使我们进行了一项处理鼠伤寒沙门氏菌感染小鼠的体内实验，并就聚氨基异戊二烯基衍生物5r /强力霉素的耐受性和有效性提供了初步有希望的结果。
更新日期：2020-09-24
中文翻译：
针对两种来自肠杆菌和沙门氏菌的多重耐药革兰氏阴性细菌的新型聚氨基异戊二烯抗生素增强剂。
根据两种合成途径，制备了一系列由新的聚氨基异戊二烯衍生物组成的化合物，其化学收率在32％至64％之间，变化范围为中度至良好：（1）使用钛还原胺化反应提供50/50的顺式和反式异构体混合物，以及2）直接亲核取代，导致目标化合物的立体选择性合成。然后成功地评估了这些化合物的体外抗生素增强剂对四种不同家族的四种抗生素的革兰氏阴性细菌的抵抗力。对抗产气肠杆菌的作用机理通过使用荧光染料测量外膜通透性并确定膜去极化，可以精确评估其中一种最有效的化学增敏剂。遇到的弱细胞毒性使我们进行了一项处理鼠伤寒沙门氏菌感染小鼠的体内实验，并就聚氨基异戊二烯基衍生物5r /强力霉素的耐受性和有效性提供了初步有希望的结果。
京公网安备 11010802027423号