lovastatin-docosahexaenoate conjugate | 1580444-10-5

• 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: lovastatin-docosahexaenoate conjugate
• 英文别名: LOV-DHA；[(2R,4R)-2-[2-[(1S,2S,6R,8S,8aR)-2,6-dimethyl-8-[(2S)-2-methylbutanoyl]oxy-1,2,6,7,8,8a-hexahydronaphthalen-1-yl]ethyl]-6-oxooxan-4-yl] (4Z,7Z,10Z,13Z,16Z,19Z)-docosa-4,7,10,13,16,19-hexaenoate
• CAS: 1580444-10-5
• 化学式: C₄₆H₆₆O₆
• 分子量: 715.026
• InChiKey: YBXHISIAIKKXFG-PJYSHWBFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  11.2
• 重原子数：
  52
• 可旋转键数：
  23
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  78.9
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  二十二碳六烯酸 、 洛伐他汀 在 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 以60.2%的产率得到lovastatin-docosahexaenoate conjugate
  参考文献：
  名称：

  Characterization of lovastatin–docosahexaenoate anticancer properties against breast cancer cells

  摘要：

  Lovastatin (LOV) and docosahexaenoic acid (DHA), besides improving cardiovascular functions, are also known for their anticancer activities. However, use of these compounds for treating or preventing cancer is limited because of their efficacies. The approach pursued involved chemical linkage of these two chemotypes. A lovastatin-docosahexaenoate (LOV-DHA) conjugate was prepared and tested against selected breast tumor cells lines with differential expression of estrogen receptors (ER) and Heregulin-2 (Her-2). The LOV-DHA conjugate exhibited superior cytotoxic effects against ER /Her-2 cell lines (MDA-MB-231 and MDA-MB-468), which were not observed with DHA or lovastatin alone, or in combination. Lovastatin supplementation arrested cells in the G(0)/G(1) phase and enhanced expression levels of p21, whereas the conjugate did not demonstrate cell cycle arrest nor increased p21 expression. The LOV-DHA conjugate induced significant (P < 0.05) apoptosis as low as 1 mu M, whereas DHA and lovastatin were ineffective at this concentration. The growth inhibitory effects of lovastatin were reversed by the addition of mevalonate, whereas mevalonate had no effect on the LOV-DHA conjugate-induced growth inhibition in MDA-MB-231 cells. Furthermore, the LOV-DHA conjugates were stable in mouse serum and intracellularly in MDA-MB-231 cells. These data suggest that the LOV-DHA conjugate mediated its effects through a HMG-CoA reductase-independent pathway and exerted significantly (P < 0.05) higher anticancer effects in breast cancer cells than lovastatin or DHA alone. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.01.051

文献信息

• Characterization of lovastatin–docosahexaenoate anticancer properties against breast cancer cells
  作者：Rafat A. Siddiqui、Kevin A. Harvey、Zhidong Xu、Selvamuthu K. Natarajan、V. Jo Davisson

  DOI：10.1016/j.bmc.2014.01.051

  日期：2014.3

  Lovastatin (LOV) and docosahexaenoic acid (DHA), besides improving cardiovascular functions, are also known for their anticancer activities. However, use of these compounds for treating or preventing cancer is limited because of their efficacies. The approach pursued involved chemical linkage of these two chemotypes. A lovastatin-docosahexaenoate (LOV-DHA) conjugate was prepared and tested against selected breast tumor cells lines with differential expression of estrogen receptors (ER) and Heregulin-2 (Her-2). The LOV-DHA conjugate exhibited superior cytotoxic effects against ER /Her-2 cell lines (MDA-MB-231 and MDA-MB-468), which were not observed with DHA or lovastatin alone, or in combination. Lovastatin supplementation arrested cells in the G(0)/G(1) phase and enhanced expression levels of p21, whereas the conjugate did not demonstrate cell cycle arrest nor increased p21 expression. The LOV-DHA conjugate induced significant (P < 0.05) apoptosis as low as 1 mu M, whereas DHA and lovastatin were ineffective at this concentration. The growth inhibitory effects of lovastatin were reversed by the addition of mevalonate, whereas mevalonate had no effect on the LOV-DHA conjugate-induced growth inhibition in MDA-MB-231 cells. Furthermore, the LOV-DHA conjugates were stable in mouse serum and intracellularly in MDA-MB-231 cells. These data suggest that the LOV-DHA conjugate mediated its effects through a HMG-CoA reductase-independent pathway and exerted significantly (P < 0.05) higher anticancer effects in breast cancer cells than lovastatin or DHA alone. (C) 2014 Elsevier Ltd. All rights reserved.