1-(3,6-dichloro-9H-carbazol-9-yl)-3-(1H-1,2,4-triazol-1-yl)propan-2-ol

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 1-(3,6-dichloro-9H-carbazol-9-yl)-3-(1H-1,2,4-triazol-1-yl)propan-2-ol
• 英文别名: 1-(3,6-Dichlorocarbazol-9-yl)-3-(1,2,4-triazol-1-yl)propan-2-ol；1-(3,6-dichlorocarbazol-9-yl)-3-(1,2,4-triazol-1-yl)propan-2-ol
• 化学式: C₁₇H₁₄Cl₂N₄O
• 分子量: 361.23
• InChiKey: AKKHEAULOASSHP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  55.9
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  9-(环氧-2-甲基)-9H-咔唑 在 N-氯代丁二酰亚胺 、 potassium carbonate 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 1-(3,6-dichloro-9H-carbazol-9-yl)-3-(1H-1,2,4-triazol-1-yl)propan-2-ol
  参考文献：
  名称：

  Potential Antimicrobial Isopropanol-Conjugated Carbazole Azoles as Dual Targeting Inhibitors of Enterococcus faecalis

  摘要：

  A series of isopropanol-bridged carbazole azoles as potential antimicrobial agents were designed and synthesized from commercial carbazoles. Bioassay revealed that 3,6-dichlorocarbazolyl triazole 3f could effectively inhibit the growth of E. faecalis with minimal inhibitory concentration of 2 mu g/mL. The active molecule 3f showed lower propensity to trigger the development of resistance in bacteria than norfloxacin and exerted rapidly bactericidal ability. Compound 3f also exhibited low cytotoxicity to normal mammalian RAW264.7 cells. Further mechanism exploration indicated that conjugate 3f was membrane active against E. faecalis and could form 3f-DNA complex by intercalating into DNA of resistant E. faecalis, which might be responsible for its antimicrobial action. Molecular docking showed an efficient binding of triazole derivative 3f with DNA gyrase enzyme through noncovalent interactions.

  DOI：

  10.1021/acsmedchemlett.7b00514

文献信息

• Elucidation of antimicrobial activity and mechanism of action by N-substituted carbazole derivatives
  作者：Johannes D. Clausen、Lasse Kjellerup、Karen O'Hanlon Cohrt、John Bondo Hansen、William Dalby-Brown、Anne-Marie L. Winther

  DOI：10.1016/j.bmcl.2017.08.067

  日期：2017.10

  to and inhibits the H+-ATPase within minutes, leading to fungal death after 1–3 h of compound exposure in vitro. The tested compounds are not selective for the fungal H+-ATPase, exhibiting an overlap of inhibitory activity with the mammalian protein family of P-type ATPases; the sarco(endo)plasmic reticulum calcium ATPase (Ca2+-ATPase) and the sodium potassium ATPase (Na+,K+-ATPase). The ion transport

  属于咔唑系列的化合物已被鉴定为有效的真菌质膜质子三磷酸腺苷酶 (H + -ATPase) 抑制剂，具有广谱抗真菌活性。咔唑化合物抑制必需真菌 H + -ATP 酶的三磷酸腺苷 (ATP) 水解活性，从而功能性地抑制质子的排出和细胞外酸化，这些过程负责维持高质膜电位。该化合物类在几分钟内结合并抑制 H + -ATP 酶，在体外暴露化合物 1-3 小时后导致真菌死亡。测试的化合物对真菌 H + -ATP 酶没有选择性，表现出与哺乳动物 P 型 ATP 酶蛋白家族重叠的抑制活性；肌（内）质网钙 ATP 酶（Ca 2+ -ATP 酶）和钠钾 ATP 酶（Na + ,K + -ATP 酶）。P 型 ATP 酶中的离子转运通过 ATP 转化为二磷酸腺苷 (ADP) 和磷酸盐来激发，因此咔唑衍生物介导的一般抑制机制可能会阻断活性位点。然而，生化研究表明，增加 ATP 浓度不会改变咔唑的抑制活性，表明它们
• Potential Antimicrobial Isopropanol-Conjugated Carbazole Azoles as Dual Targeting Inhibitors of <i>Enterococcus faecalis</i>
  作者：Yuan Zhang、Vijai Kumar Reddy Tangadanchu、Yu Cheng、Ren-Guo Yang、Jian-Mei Lin、Cheng-He Zhou

  DOI：10.1021/acsmedchemlett.7b00514

  日期：2018.3.8

  A series of isopropanol-bridged carbazole azoles as potential antimicrobial agents were designed and synthesized from commercial carbazoles. Bioassay revealed that 3,6-dichlorocarbazolyl triazole 3f could effectively inhibit the growth of E. faecalis with minimal inhibitory concentration of 2 mu g/mL. The active molecule 3f showed lower propensity to trigger the development of resistance in bacteria than norfloxacin and exerted rapidly bactericidal ability. Compound 3f also exhibited low cytotoxicity to normal mammalian RAW264.7 cells. Further mechanism exploration indicated that conjugate 3f was membrane active against E. faecalis and could form 3f-DNA complex by intercalating into DNA of resistant E. faecalis, which might be responsible for its antimicrobial action. Molecular docking showed an efficient binding of triazole derivative 3f with DNA gyrase enzyme through noncovalent interactions.