(2S)-N-[(2S)-6-ethanethioylamino-1-(phenylamino)-1-oxohexan-2-yl]-pyrrolidine-2-carboxamide hydrochloride | 1450838-04-6

• 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: (2S)-N-[(2S)-6-ethanethioylamino-1-(phenylamino)-1-oxohexan-2-yl]-pyrrolidine-2-carboxamide hydrochloride
• 英文别名: H-Pro-Lys(TAc)-NHPh.HCl；(2S)-N-[(2S)-1-anilino-6-(ethanethioylamino)-1-oxohexan-2-yl]pyrrolidine-2-carboxamide;hydrochloride
• CAS: 1450838-04-6
• 化学式: C₁₉H₂₈N₄O₂S*ClH
• 分子量: 412.984
• InChiKey: ZGQXOUWNJWNUKX-QJHJCNPRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.39
• 重原子数：
  27
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  114
• 氢给体数：
  5
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  (2S)-N-[(2S)-6-ethanethioylamino-1-phenylamino-1-oxohexan-2-yl]pyrrolidine-1-tertbutoxycarbonyl-2-carboxamide 在 盐酸 、 1,2-乙二硫醇 作用下， 以 异丙醇 为溶剂， 反应 2.0h， 以85%的产率得到(2S)-N-[(2S)-6-ethanethioylamino-1-(phenylamino)-1-oxohexan-2-yl]-pyrrolidine-2-carboxamide hydrochloride
  参考文献：
  名称：

  Screen of Pseudopeptidic Inhibitors of Human Sirtuins 1–3: Two Lead Compounds with Antiproliferative Effects in Cancer Cells

  摘要：

  In the past few years sirtuins have gained growing attention for their involvement in many biological processes such as cellular metabolism, apoptosis; aging and inflammation. In this contribution, we report the synthesis of a library of thioacetylated pseudopeptides that were screened against human sirtuins 1-3 to reveal their in vitro inhibition activities. Molecular modeling studies were performed to acquire data about the binding modes of the inhibitors. Three sirtuin inhibitors were subjected to cellular studies, and all of them showed an increase in acetylation of Lys382 of p53 after DNA damage. Furthermore, two of the compounds were able to inhibit both A549 lung carcinoma and MCF-7 breast carcinoma cell growth in micromolar concentration with the ability to arrest cancer cell cycle in the GI phase.

  DOI：

  10.1021/jm400438k

文献信息

• Screen of Pseudopeptidic Inhibitors of Human Sirtuins 1–3: Two Lead Compounds with Antiproliferative Effects in Cancer Cells
  作者：Paolo Mellini、Tarja Kokkola、Tiina Suuronen、Heikki S. Salo、Laura Tolvanen、Antonello Mai、Maija Lahtela-Kakkonen、Elina M. Jarho

  DOI：10.1021/jm400438k

  日期：2013.9.12

  In the past few years sirtuins have gained growing attention for their involvement in many biological processes such as cellular metabolism, apoptosis; aging and inflammation. In this contribution, we report the synthesis of a library of thioacetylated pseudopeptides that were screened against human sirtuins 1-3 to reveal their in vitro inhibition activities. Molecular modeling studies were performed to acquire data about the binding modes of the inhibitors. Three sirtuin inhibitors were subjected to cellular studies, and all of them showed an increase in acetylation of Lys382 of p53 after DNA damage. Furthermore, two of the compounds were able to inhibit both A549 lung carcinoma and MCF-7 breast carcinoma cell growth in micromolar concentration with the ability to arrest cancer cell cycle in the GI phase.