Design, synthesis, and biological evaluation of novel carbazole aminothiazoles as potential DNA-targeting antimicrobial agents
Design, synthesis, and biological evaluation of novel carbazole aminothiazoles as potential DNA-targeting antimicrobial agents
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作为潜在 DNA 靶向抗菌剂的新型咔唑氨基噻唑的设计、合成和生物学评价
DOI：
10.1039/c6md00357e
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发表时间：
2016-01-01
期刊：
影响因子：
--
通讯作者：
Zhou, Cheng-He
中科院分区：
文献类型：
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作者：
Addla, Dinesh;Wen, Si-Qi;Zhou, Cheng-He
设计、合成了一系列新型咔唑氨基噻唑类新型抗菌剂，并通过氢 -1核磁共振、碳 -13核磁共振、红外光谱、质谱和高分辨率质谱进行了表征。一些咔唑氨基噻唑表现出良好的抗菌活性；特别是庚基衍生的咔唑氨基噻唑4f能有效抑制耐甲氧西林金黄色葡萄球菌（MRSA）的生长，其最小抑菌浓度（MIC）值为4微克/毫升，优于对照药物氯霉素和诺氟沙星。此外，细胞毒性研究表明，生物活性化合物4f在其对MRSA的MIC范围内对Hep - 2细胞没有细胞毒性。初步的相互作用研究显示，化合物4f能有效地嵌入小牛胸腺DNA中形成4f - DNA复合物，这可能会阻断DNA复制，从而发挥抗菌活性。此外，化合物4f与DNA的结合行为表明，化合物4f可通过氢键和静电相互作用与DNA相互作用。
A series of novel carbazole aminothiazoles as a new type of antimicrobial agents were designed, synthesized and characterized by 1H NMR, 13C NMR, IR, MS and HRMS spectra. Some of the carbazole aminothiazoles exhibited good antimicrobial activities; particularly, heptyl-derived carbazole aminothiazole 4f could effectively inhibit the growth of MRSA with an MIC value of 4 μg mL−1, which was superior to the reference drugs Chloromycin and Norfloxacin. Moreover, cytotoxicity investigation indicated that bioactive compound 4f did not exhibit cytotoxicity to Hep-2 cells within its MIC against MRSA. Preliminary interactive investigation revealed that compound 4f could effectively intercalate into calf thymus DNA to form 4f–DNA complexes which might block DNA replication and thus exert antimicrobial activities. In addition, the binding behavior of compound 4f to DNA revealed that compound 4f could interact with DNA by hydrogen bonds and electrostatic interactions.