Novel carbazole-oxadiazoles as potential Staphylococcus aureus germicides
Novel carbazole-oxadiazoles as potential Staphylococcus aureus germicides
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新型咔唑-恶二唑作为潜在的金黄色葡萄球菌杀菌剂
DOI：
10.1016/j.pestbp.2021.104849
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发表时间：
2021-05-13
影响因子：
4.7
通讯作者：
Zhou, Cheng-He
中科院分区：
文献类型：
--
作者：
Xie, Yun-Peng;Ansari, Mohammad Fawad;Zhou, Cheng-He
金黄色葡萄球菌耐药性对畜牧业构成不可忽视的威胁。鉴于此，设计并合成了咔唑恶二唑类化合物。金黄色葡萄球菌感染。生物活性测定结果表明，3，6-二溴咔唑衍生物13 a对多种革兰氏阳性菌，尤其是对S.金黄色葡萄球菌、金黄色葡萄球菌ATCC 29213、耐甲氧西林金黄色葡萄球菌和链球菌。金黄色葡萄球菌ATCC 25923（MIC = 0.6-4.6 nmol/mL）比诺氟沙星（MIC = 6-40 nmol/mL）更有效。随后的研究表明，3，6-二溴咔唑衍生物13 a对S.金黄色葡萄球菌ATCC 29213，没有明显的诱导细菌耐药性的趋势。进一步研究表明，3，6-二溴咔唑衍生物13 a具有较强的生物膜破坏能力和DNA干扰能力，这可能是其抗菌性能的动力来源。此外，3，6-二溴咔唑衍生物13 a对Hek 293 T和LO 2细胞也显示出轻微的细胞致死性，对红细胞的溶血毒性低。以上结果表明，活性分子13 a可作为农用抗生素开发的研究对象。
Staphylococcus aureus resistance poses nonnegligible threats to the livestock industry. In light of this, carbazoleoxadiazoles were designed and synthesized for treating S. aureus infection. Bioassay discovered that 3,6-dibromocarbazole derivative 13a had effective inhibitory activities to several Gram-positive bacteria, in particular to S. aureus, S. aureus ATCC 29213, MRSA and S. aureus ATCC 25923 (MICs = 0.6-4.6 nmol/mL), which was more active than norfloxacin (MICs = 6-40 nmol/mL). Subsequent studies showed that 3,6-dibromocarbazole derivative 13a acted rapidly on S. aureus ATCC 29213 and possessed no obvious tendency to induce bacterial resistance. Further evaluations indicated that 3,6-dibromocarbazole derivative 13a showed strong abilities to disrupt bacterial biofilm and interfere with DNA, which might be the power sources of antibacterial performances. Moreover, 3,6-dibromocarbazole derivative 13a also exhibited slight cell lethality toward Hek 293 T and LO2 cells and low hemolytic toxicity to red blood cells. The above results implied that the active molecule 13a could be studied in the future development of agricultural available antibiotics.