L-FDLA-L-Met | 199729-70-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: L-FDLA-L-Met
• CAS: 199729-70-9
• 化学式: C₁₇H₂₅N₅O₇S
• 分子量: 443.481
• InChiKey: ZPOPFZJIZFZJOQ-GWCFXTLKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.43
• 重原子数：
  30.0
• 可旋转键数：
  13.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  190.73
• 氢给体数：
  4.0
• 氢受体数：
  9.0

反应信息

• 作为产物：
  描述：

  thailandepsin A 、 NAlpha-(5-氟-2,4-二硝基苯基)-L-亮氨酰胺 在 盐酸 、 水 、 碳酸氢钠 作用下， 以 水 、 丙酮 、 乙腈 为溶剂， 反应 25.0h， 生成 L-FDLA-L-Met
  参考文献：
  名称：

  Thailandepsins: Bacterial Products with Potent Histone Deacetylase Inhibitory Activities and Broad-Spectrum Antiproliferative Activities

  摘要：

  Histone deacetylase (HDAC) inhibitors have emerged as a new class of anticancer drugs, with one synthetic compound, SAHA (vorinostat, Zolinza; 1), and one natural product, FK228 (depsipeptide, romidepsin, Istodax; 2), approved by FDA for clinical use. Our studies of FK228 biosynthesis in Chromobacterium violaceum no. 968 led to the identification of a cryptic biosynthetic gene cluster in the genome of Burkholderia thailandensis E264. Genome mining and genetic manipulation of this gene cluster further led to the discovery of two new products, thailandepsin A (6) and thailandepsin B (7). HDAC inhibition assays showed that thailandepsins have selective inhibition profiles different from that of FK228, with comparable inhibitory activities to those of FK228 toward human HDAC1, HDAC2, HDAC3, HDAC6, HDAC7, and HDAC9 but weaker inhibitory activities than FK228 toward HDAC4 and HDAC8, the latter of which could be beneficial. NCI-60 anticancer screening assays showed that thailandepsins possess broad-spectrum antiproliferative activities with GI(50) for over 90% of the tested cell lines at low nanomolar concentrations and potent cytotoxic activities toward certain types of cell lines, particularly for those derived from colon, melanoma, ovarian, and renal cancers. Thailandepsins thus represent new naturally produced HDAC inhibitors that are promising for anticancer drug development.

  DOI：

  10.1021/np200324x

文献信息

• Oryzamides A–E, Cyclodepsipeptides from the Sponge-Derived Fungus <i>Nigrospora oryzae</i> PF18
  作者：Li-Jian Ding、Wei Yuan、Xiao-Jian Liao、Bing-Nan Han、Shu-Ping Wang、Zhi-Yong Li、Shi-Hai Xu、Wei Zhang、Hou-Wen Lin

  DOI：10.1021/acs.jnatprod.6b00349

  日期：2016.8.26

  new cyclohexadepsipeptides, oryzamides A–C (1–3), two isolation artifacts, oryzamides D (4) and E (5), and the known congener scopularide A (6), all possessing a rare 3-hydroxy-4-methyldecanoic acid (HMDA) substructure, were isolated from the mycelial extract of the sponge-derived fungus Nigrospora oryzae PF18. Their planar structures were elucidated by spectroscopic analysis and comparison with the literature

  三个新的环己缩，oryzamides A-C（1 - 3），两个隔离构件，oryzamides d（4）和E（5），和已知的同类scopularide A（6），所有具有罕见的3-羟基-4- methyldecanoic从海绵衍生的真菌Nigrospora oryzae PF18的菌丝体提取物中分离出乙酸（HMDA）亚结构。通过光谱分析和与文献数据的比较阐明了它们的平面结构。绝对构型使用先进的Marfey方法和单晶X射线衍射分析确定。其中，谷维酰胺D（4）和E（5）是在1-甲硫氨酸亚砜残基的硫原子上的一对非对映异构体，这表明可能分离出一对甲硫氨酸亚砜非对映异构体。首次获得了cop石甲A（6）的X射线晶体结构，从而确定了其在HMDA残基C-4处的相对和绝对构型。Oryzamides A-C（1 - 3）不显示细胞毒性，抗细菌，抗寄生虫，和NF-κB的抑制活性。