N-hydroxy-4-oxo-3-oxa-13-azatetracyclo[7.7.1.02,7.013,17]heptadeca-1,5,7,9(17)-tetraene-5-carboxamide | 1061241-93-7

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 香豆素及其衍生物
• 英文名称: N-hydroxy-4-oxo-3-oxa-13-azatetracyclo[7.7.1.02,7.013,17]heptadeca-1,5,7,9(17)-tetraene-5-carboxamide
• CAS: 1061241-93-7
• 化学式: C₁₆H₁₆N₂O₄
• 分子量: 300.314
• InChiKey: LWIAZVGDVPLCJN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  22
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  78.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  sodium tris(carbonato)cobaltate(III) 、 N-hydroxy-4-oxo-3-oxa-13-azatetracyclo[7.7.1.02,7.013,17]heptadeca-1,5,7,9(17)-tetraene-5-carboxamide 、 6,6′-(pyridine-2-ylmethylazanediyl)bis(methylene)dinicotinic acid 在 高氯酸 作用下， 以 甲醇 、 水 为溶剂， 反应 2.0h， 以66%的产率得到
  参考文献：
  名称：

  钴（III）分子伴侣配合物在低氧和酸性肿瘤环境中的双重靶向

  摘要：

  在肿瘤微环境中选择性积聚和活化的前药的合理设计是使抗癌药物的毒性最小化的最有希望的策略之一。对前药电荷的操纵代表了将前药选择性地递送至酸性肿瘤微环境的潜在机制。在这里，我们介绍使用钴（III）伴侣分子靶向低氧区域的荧光香豆素，以及带电配体的pH选择性。在生理相关的pH范围内，复合物的质子化或去质子化导致荧光团在结肠癌细胞中的pH依赖性积累。此外，在球状实体瘤模型中，阴离子络合物在酸性/低氧区域表现出荧光团的优先释放。

  DOI：

  10.1021/jm3014713

文献信息

• New Peptides with Metal Binding Abilities and Their Use as Drug Carriers
  作者：Anas Allam、Laure Maigre、Mickael Alimi、Rodolphe Alves de Sousa、Assia Hessani、Erwan Galardon、Jean-Marie Pagès、Isabelle Artaud

  DOI：10.1021/bc500317u

  日期：2014.10.15

  Many new designed molecules that target efficiently in vitro bacterial metalloproteases were completely inactive in cellulo against Gram negative bacteria. Their activities were limited by the severe restriction of the penetration/diffusion rate through the outer membrane barrier. To bypass this limitation, we have assayed the strategy of metallodrugs, to improve the delivery of hydroxamic acid inhibitors to peptide deformylase. In this metal-chaperone, to facilitate bacterial uptake, the ancillary ligand tris(2-pyridylmethyl)amine (TPA) or di(picolyl)amine (DPA) was functionalized by a tetrapeptide analogue of antimicrobial peptide, RWRW(OBn) (AA08 with TPA) and/or an efflux pump modulator PA beta N (AA09 with TPA and AA27 with DPA). We prepared Co(III), Zn(II), and Cu(II) metallodrugs. Using a fluorescent hydroxamic acid, we showed that, in contrast to Cu(II) metallodrugs, Co(III) metallodrugs were stable in the Mueller Hinton (MH) broth during the time required for bacterial assays. The antibacterial activities were determined against E. coli strain wild-type (AG100) and E. coli strain deleted from acrAB efflux pump (AG100A). While none of the PDFinhs used in this study (SMP289 with an indole scaffold, AT015 and AT019 built on a 1,2,4-oxadiazole scaffold) displayed activity higher than 128 mu M, all the metallodrugs were active with MICs around 8 mu M both against AG100 and AG100A. However, compared to the activities of equimolar combinations of PDFinhs and the free chelating peptides (AA08, AA09, or AA27), they showed similar activities. A synergistic association between AT019 and AA08 or AA09 was determined using the fractional inhibitory concentration with AG100 and AG100A. Combinations of peptides lacking the chelating group with PDFinhs were inefficient. LC-MS analyses showed that the chelating peptides bind Zn(II) cation when incubated in MH broth. These results support the in situ formation of a zinc metallodrug, but we failed to detect it by LC-MS in MH. Nevertheless, this chelating peptides metalated with zinc act as permeabilizers which are more efficient than PA beta N to facilitate the uptake of PDFinhs by Gram(-) bacteria.