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评价倍半萜类化合物的致突变性及其对两种临床相关细菌菌株对抗生素敏感性的影响。

Evaluation of the mutagenicity of sesquiterpenic compounds and their influence on the susceptibility towards antibiotics of two clinically relevant bacterial strains.

机构信息

Departamento de Química, Universidade de Aveiro, Aveiro, Portugal.

出版信息

Mutat Res. 2011 Jul 14;723(1):18-25. doi: 10.1016/j.mrgentox.2011.03.010. Epub 2011 Mar 29.

Abstract

Sesquiterpenic compounds are natural chemicals present in organisms from different Phylae or Divisions, which have proved to be important bioactive products, namely in potentiating the action of antibiotics. In the first step, the mutagenicity of nine sesquiterpenic compounds (hydrocarbons and alcohols) was screened in a Salmonella typhimurium his(-)-reversion test with strains TA98 and TA100, in the presence or absence of in vitro metabolic activation. Under the test conditions, none of the compounds showed mutagenicity up to a concentration of 222μg/plate. trans-Farnesol, nerolidol, and α-bisabolol displayed cytotoxicity when tested at concentrations ranging from 14 to 222μg/plate. Then, the combined effect of antibiotic-sesquiterpenic compounds was evaluated on two clinically relevant pathogens, Escherichia coli and Staphylococcus aureus, with well-defined resistance-sensitive profiles. The agar-disc diffusion assay revealed that all the combinations of antibiotic-sesquiterpenic compounds increased the antibacterial activity of the antibiotics tested against S. aureus. For E. coli, an antagonistic effect was observed for various combinations on the growth of this bacterium.

摘要

倍半萜类化合物是存在于不同门或界的生物体中的天然化学物质,已被证明是重要的生物活性产物,特别是在增强抗生素的作用方面。在第一步中,使用含有或不含有体外代谢活化的 TA98 和 TA100 菌株,在鼠伤寒沙门氏菌 his(-)-回复试验中筛选了九种倍半萜类化合物(碳氢化合物和醇类)的诱变活性。在试验条件下,这些化合物在高达 222μg/平板的浓度下均未显示出诱变活性。当在 14 至 222μg/平板的浓度下测试时,反式法呢醇、橙花叔醇和 α- 双醇显示出细胞毒性。然后,评估了抗生素-倍半萜类化合物对两种具有明确耐药敏感谱的临床相关病原体大肠杆菌和金黄色葡萄球菌的联合作用。琼脂扩散试验显示,抗生素-倍半萜类化合物的所有组合均增加了测试抗生素对金黄色葡萄球菌的抗菌活性。对于大肠杆菌,观察到各种组合对该细菌生长的拮抗作用。

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