Khellacton | 518-76-3

• 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: Khellacton
• 英文别名: khellactone；3',4'-Dihydroxy-3',4'-dihydro-seselin；9,10-dihydroxy-8,8-dimethyl-9,10-dihydropyrano[2,3-f]chromen-2-one
• CAS: 518-76-3；4968-31-4；15575-68-5；15645-11-1；20516-17-0；23458-04-0；24144-61-4；54712-23-1；80124-45-4
• 化学式: C₁₄H₁₄O₅
• 分子量: 262.262
• InChiKey: HKXQUNNSKMWIKJ-UHFFFAOYSA-N

物化性质

• 熔点：
  86-88 °C(Solv: methanol (67-56-1))
• 沸点：
  165 °C(Press: 20 Torr)
• 密度：
  1.399±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  19
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  76
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  Khellacton 、 4-甲基-2-氧代戊酸 生成 3',4'-diisovalerylkhellactone
  参考文献：
  名称：

  BAL-TEMBE, SWATI;BHEDI, DILIP N.;SOUZA, NOEL J. DE;RUPP, RICHARD HELMUT, HETEROCYCLES, 26,(1987) N 5, 1239-1249

  摘要：

  DOI：
• 作为产物：
  描述：

  邪蒿素 生成 Khellacton
  参考文献：
  名称：

  BAL-TEMBE, SWATI;BHEDI, DILIP N.;SOUZA, NOEL J. DE;RUPP, RICHARD HELMUT, HETEROCYCLES, 26,(1987) N 5, 1239-1249

  摘要：

  DOI：

文献信息

• 3′-O, 4′-O-aromatic acyl substituted 7,8-pyranocoumarins: a new class of P-glycoprotein modulators
  作者：Xiaoling Shen、Guangying Chen、Guoyuan Zhu、Jiazhong Cai、Lu Wang、Yingjie Hu、Wang-Fun Fong

  DOI：10.1111/j.2042-7158.2011.01378.x

  日期：2011.12.8

  P-glycoprotein (Pgp) overexpression in tumour cells leads to multidrug resistance (MDR) and causes failure in cancer chemotherapy. We have previously identified (±)-praeruptorin A (PA) as a potential lead compound for Pgp modulators. In this study we investigated the MDR-reversing activities of PA derivatives.

  Series 7,8-pyranocoumarins with various C-3′ and C-4′ side chains had been semi-synthesized and their MDR-reversing activity was investigated in Pgp-overexpressing MDR tumour cell line HepG2/Dox and in a KB V1 xenograft animal model.

  All 7,8-pyranocoumarins exhibited equal or higher activity in modulating Pgp. DCK (12), DMDCK (15), 16, 21, 23 and 24 at 4 µm achieved 91%∼99% decrease in IC50 value (concentration inhibiting cell growth by 50%) of anticancer agents vinblastine, doxorubicin, puromycin and paclitaxel, and were more active than others. DMDCK also remarkably enhanced the growth inhibitory effect of paclitaxel on KB V1 xenografts (P < 0.05), showing a potency required for clinical usage. Mechanistic studies suggested that these 7,8-pyranocoumarins might reverse Pgp-MDR through directly binding to substrate binding site(s) or allosteric site(s) on Pgp therefore impairing Pgp-mediated drug transport.

  Results from the study suggested that 3′-O, 4′-O-aromatic acyl substituted 7,8-pyranocoumarins could serve as a new class of Pgp modulator. Acyls play an important role in maintaining and enhancing the Pgp-modulating ability of pyranocoumarins. 3,4-Dimethoxyl substituted aromatic acyls, bearing a methoxy that might interact with Pgp as hydrogen bond accepter, were shown to be the most potent for reversing MDR.

  摘要：本研究旨在探讨(±)-praeruptorin A (PA)衍生物的多药耐药（MDR）逆转活性。我们发现，所有7,8-吡喃香豆素在调节Pgp方面表现出相等或更高的活性。其中DCK（12）、DMDCK（15）、16、21、23和24在4微米时，可以使抗癌药物长春新碱、阿霉素、普鲁霉素和紫杉醇的IC50值（抑制细胞生长50%的浓度）降低91%∼99%，比其他衍生物更活跃。DMDCK还显著增强了对KB V1异种移植动物模型中紫杉醇的生长抑制作用（P < 0.05），表现出临床应用所需的效力。机制研究表明，这些7,8-吡喃香豆素可能通过直接结合Pgp的底物结合位点或变构位点，从而损害Pgp介导的药物转运，逆转Pgp-MDR。研究结果表明，3′-O、4′-O-芳基酰基取代的7,8-吡喃香豆素可以作为一类新型Pgp调节剂。酰基在维持和增强吡喃香豆素的Pgp调节能力中起着重要作用。3,4-二甲氧基取代的芳基酰基，具有一个可能与Pgp作为氢键受体相互作用的甲氧基，被证明是最有效的逆转MDR。
• Antidiabetic effect, antioxidant activity, and toxicity of 3′,4′-Di-O-acetyl-cis-khellactone in Streptozotocin-induced diabetic rats
  作者：Elix Alberto Domínguez-Mendoza、Jorge Cornejo-Garrido、Eleuterio Burgueño-Tapia、Cynthia Ordaz-Pichardo

  DOI：10.1016/j.bmcl.2016.06.071

  日期：2016.8

  Pyranocoumarins are compounds with an important pharmacological profile, such as anti-inflammatory, antioxidant, cytotoxic, antiviral, antibacterial, and hypoglycemic effects. These molecules have a widespread presence as secondary metabolites in medicinal plants used to treat Diabetes Mellitus (DM). The aim of this work was to evaluate antidiabetic activity in Streptozotocin (STZ)-induced diabetic rats and the antioxidant effects of 3',4'-Di-O-acetyl-cis-khellactone (DOAcK), as well as its toxic potential. We obtained DOAcK with an enantiomeric excess of 70% by chemical synthesis. Our results showed that this compound exerts an important antidiabetic effect: blood glucose decreased in groups treated with DOAcK by 60.9% at dose of 15 mg/kg (p <0.05) compared with the diabetic control group, and demonstrated a statistically significant increase in weight gain (45.7 +/- 9.7 in the group treated with DOAcK vs. -23.0 +/- 33.1 in the group with diabetes). In a biochemical profile, DOAcK did not modify lipid metabolism and did not cause damage at the renal level. DOAcK administration increased the activities of Catalase (CAT), Glutathione Peroxidase (GPx), and Super Oxide Dismutase (SOD) to levels near those of the healthy group. Histopathological analysis exhibited morphology similar to that of the healthy group and the group treated with DOAcK. DOAcK is not mutagenic by Ames test for Salmonella typhimurium strains TA98, TA100, or TA102, and is not genotoxic by Micronucleus assay; median lethal dose (LD50) >2000 mg/kg and, at this dose, no signs of toxicity or death were reported after 14 days of observation. These results indicate that DOAcK can improve glucose metabolism, which may be due to the increased antioxidant activity of CAT, GPx and SOD. In addition, DOAcK is not toxic in the studies tested. (C) 2016 Elsevier Ltd. All rights reserved.
• BAL-TEMBE, SWATI;BHEDI, DILIP N.;SOUZA, NOEL J. DE;RUPP, RICHARD HELMUT, HETEROCYCLES, 26,(1987) N 5, 1239-1249
  作者：BAL-TEMBE, SWATI、BHEDI, DILIP N.、SOUZA, NOEL J. DE、RUPP, RICHARD HELMUT

  DOI：——

  日期：——