柳酰苯胺基甲酸酯类化合物：具有抗分枝杆菌活性的抗结核药物，可有效对抗耐多药结核分枝杆菌菌株。

Salicylanilide carbamates: antitubercular agents active against multidrug-resistant Mycobacterium tuberculosis strains.

机构信息

Department of Inorganic and Organic Chemistry, Faculty of Pharmacy, Charles University, Heyrovského 1203, 500 05 Hradec Králové, Czech Republic.

出版信息

Bioorg Med Chem. 2010 Feb;18(3):1054-61. doi: 10.1016/j.bmc.2009.12.055. Epub 2009 Dec 29.

DOI:10.1016/j.bmc.2009.12.055

PMID:20060303

Abstract

A series of 27 salicylanilide-based carbamates was prepared as a part of our ongoing search for new antituberculosis drugs. These compounds exhibited very good in vitro activity against Mycobacterium tuberculosis, Mycobacterium kansasii and Mycobacterium avium and, in particular, against five multidrug-resistant strains, with MIC values between 0.5-2 micromol/L. Moreover, they displayed moderate toxicity against intestinal cells with the selectivity index being up to 96. Furthermore, acid stability and a half-life of 43h at pH 7.4 were shown. Thus, these novel salicylanilide derivatives are drug candidates which should be seriously consider for further screening.

摘要

作为我们正在进行的寻找新的抗结核药物的一部分，我们合成了一系列 27 种水杨酰苯胺基氨基甲酸酯。这些化合物对结核分枝杆菌、堪萨斯分枝杆菌和鸟分枝杆菌表现出非常好的体外活性，特别是对五种耐多药菌株，MIC 值在 0.5-2 微摩尔/升之间。此外，它们对肠道细胞显示出中等毒性，选择性指数高达 96。此外，还显示出在 pH7.4 时的酸稳定性和半衰期为 43 小时。因此，这些新型水杨酰苯胺基衍生物是候选药物，应进一步筛选。