Patel Mohit, Negin Saeedeh, Meisel Joseph, Yin Shanheng, Gokel Michael, Gill Hannah, Gokel George
Department of Chemistry & Biochemistry, University of Missouri, St. Louis, MO 63121, USA.
Department of Biology, University of Missouri, St. Louis, MO 63121, USA.
Antibiotics (Basel). 2021 Nov 12;10(11):1391. doi: 10.3390/antibiotics10111391.
The compounds referred to as (tryptophan)s (BTs) have shown activity as antimicrobials. The hypothesis that the activity of these novel amphiphiles results from insertion in bilayer membranes and transport of cations is supported by planar bilayer voltage-clamp studies reported herein. In addition, fluorescence studies of propidium iodide penetration of vital bacteria confirmed enhanced permeability. It was also found that BTs having either meta-phenylene or n-dodecylene linkers function as effective adjuvants to enhance the properties of FDA-approved antimicrobials against organisms such as . In one example, a BT-mediated synergistic effect enhanced the potency of norfloxacin against by 128-fold. In order to determine if related compounds in which tryptophan was replaced by other common amino acids (HN-Aaa-linker-Aaa-NH) we active, a family of analogs have been prepared, characterized, and tested as controls for both antimicrobial activity and as adjuvants for other antimicrobials against both Gram-negative and Gram-positive bacteria. The most active of the compounds surveyed remain the bis(tryptophan) derivatives.
被称为（色氨酸）（BTs）的化合物已显示出抗菌活性。本文报道的平面双层电压钳研究支持了这样一种假设，即这些新型两亲物的活性源于其插入双层膜并转运阳离子。此外，对碘化丙啶穿透活细菌的荧光研究证实了通透性增强。还发现具有间亚苯基或正十二烯连接基的BTs可作为有效的佐剂，增强美国食品药品监督管理局（FDA）批准的抗菌剂对诸如……等生物体的性能。在一个实例中，BT介导的协同效应使诺氟沙星对……的效力提高了128倍。为了确定色氨酸被其他常见氨基酸取代的相关化合物（HN - Aaa - 连接基 - Aaa - NH）是否具有活性，已制备、表征并测试了一系列类似物，作为抗菌活性的对照以及作为其他抗菌剂针对革兰氏阴性菌和革兰氏阳性菌的佐剂。在所研究的化合物中，活性最高的仍然是双（色氨酸）衍生物。
