新型抗多重耐药结核分枝杆菌及其他微生物的水杨酸苯胺酯类衍生物。
New amino acid esters of salicylanilides active against MDR-TB and other microbes.
机构信息
Department of Inorganic and Organic Chemistry, Faculty of Pharmacy, Charles University, and Department of Clinical Microbiology, University Hospital, Heyrovského 1203, 500 05 Hradec Králové, Czech Republic.
出版信息
Eur J Med Chem. 2010 Dec;45(12):6106-13. doi: 10.1016/j.ejmech.2010.09.040.
Eleven halogenated (S)-2-(phenylcarbamoyl)phenyl 2-acetamido-3-phenylpropanoates (3a-3k) were designed and synthesized as potential antimicrobial agents. They were evaluated in vitro against some mycobacterial, bacterial and fungal strains. These compounds were active against drug-sensitive and atypical mycobacterial strains with general MIC values from 0.25 to 16 μmol/L. The most active compounds were (S)-4-chloro-2-(4-(trifluoromethyl)phenylcarbamoyl)phenyl 2-acetamido-3-phenylpropanoate (3i) and (S)-4-bromo-2-(4-(trifluoromethyl)phenylcarbamoyl)phenyl 2-acetamido-3-phenylpropanoate (3k) which exhibited activity against MDR and XDR-TB strains with MICs from 1 to 2 μmol/L. 3k was shown to be less cytotoxic with higher IC50. Some compounds exhibited low MICs on Gram-positive bacteria (MICs≥0.98 μmol/L) and on fungi (MICs≥3.9 μmol/L).
设计并合成了 11 种卤代（S）-2-（苯甲酰胺基）苯基 2-乙酰氨基-3-苯基丙酸盐（3a-3k）作为潜在的抗菌剂。对它们进行了体外抗一些分枝杆菌、细菌和真菌菌株的活性评价。这些化合物对药敏和非典型分枝杆菌菌株均具有活性，一般 MIC 值为 0.25 至 16 μmol/L。最具活性的化合物为（S）-4-氯-2-（4-（三氟甲基）苯甲酰胺基）苯基 2-乙酰氨基-3-苯基丙酸盐（3i）和（S）-4-溴-2-（4-（三氟甲基）苯甲酰胺基）苯基 2-乙酰氨基-3-苯基丙酸盐（3k），它们对 MDR 和 XDR-TB 菌株的 MIC 值为 1 至 2 μmol/L。3k 的细胞毒性较低，IC50 较高。一些化合物对革兰氏阳性菌（MICs≥0.98 μmol/L）和真菌（MICs≥3.9 μmol/L）的 MIC 值较低。
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