新型 5'-去环丙基嘧啶衍生物作为抗菌剂。

Novel 5'-Norcarbocyclic Pyrimidine Derivatives as Antibacterial Agents.

机构信息

Engelhardt Institute of Molecular Biology of the Russian Academy of Sciences, 32 Vavilov St., Moscow 119991, Russia.

Gause Institute of New Antibiotics, 11 Bol'shaya Pirogovskaya St., Moscow 119021, Russia.

出版信息

Molecules. 2018 Nov 23;23(12):3069. doi: 10.3390/molecules23123069.

A series of novel 5'-norcarbocyclic derivatives of 5-alkoxymethyl or 5-alkyltriazolyl-methyl uracil were synthesized and the activity of the compounds evaluated against both Gram-positive and Gram-negative bacteria. The growth of was completely inhibited by the most active compounds at a MIC of 67 μg/mL (mc²155) and a MIC of 6.7⁻67 μg/mL (VKPM Ac 1339). Several compounds also showed the ability to inhibit the growth of attenuated strains of ATCC 25177 (MIC 28⁻61 μg/mL) and ATCC 35737 (MIC 50⁻60 μg/mL), as well as two virulent strains of ; a laboratory strain H37Rv (MIC 20⁻50 μg/mL) and a clinical strain with multiple drug resistance MS-115 (MIC 20⁻50 μg/mL). Transmission electron microscopy (TEM) evaluation of H37Rv bacterial cells treated with one of the compounds demonstrated destruction of the bacterial cell wall, suggesting that the mechanism of action for these compounds may be related to their interactions with bacteria cell walls.

我们合成了一系列新型 5'-去环丙基 5-烷氧甲基或 5-烷基三唑基甲基尿嘧啶衍生物，并评估了它们对革兰氏阳性菌和革兰氏阴性菌的活性。最活跃的化合物在 MIC 为 67 μg/mL（mc²155）和 MIC 为 6.7⁻67 μg/mL（VKPM Ac 1339）时完全抑制了的生长。几种化合物还显示出抑制 ATCC 25177（MIC 28⁻61 μg/mL）和 ATCC 35737（MIC 50⁻60 μg/mL）减毒菌株生长的能力，以及两种毒力菌株的生长；实验室菌株 H37Rv（MIC 20⁻50 μg/mL）和具有多种耐药性的临床菌株 MS-115（MIC 20⁻50 μg/mL）。用其中一种化合物处理 H37Rv 细菌细胞的透射电子显微镜（TEM）评估表明，细菌细胞壁被破坏，这表明这些化合物的作用机制可能与其与细菌细胞壁的相互作用有关。