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新型 5-氟-N-(9,10-二氢-9,10-二氧代蒽-8-基)-1H-吲哚-2-甲酰胺衍生物对 Triton-WR-1339 诱导的 Wistar 大鼠血脂谱的药理学作用。

The pharmacological effects of novel 5-fluoro-N-(9,10-dihydro-9,10-dioxoanthracen-8-yl)-1H-indole-2-carboxamide derivatives on plasma lipid profile of Triton-WR-1339-induced Wistar rats.

机构信息

Faculty of Pharmacy, Al-Zaytoonah University of Jordan, Amman, Jordan.

出版信息

J Enzyme Inhib Med Chem. 2013 Aug;28(4):863-9. doi: 10.3109/14756366.2012.692085. Epub 2012 May 31.

Abstract

A novel series of 5-fluoro-N-(9,10-dihydro-9,10-dioxoanthracen-8-yl)-1H-indole-2-carboxamides (3c-3g) were synthesized. The present study was undertaken to investigate the possible antihyperlipidemic effect of these novel compounds on hyperlipidemic rats. Hyperlipidemia was induced by a single intraperitoneal injection of Triton WR-1339 (300 mg/kg). The tested animals were divided into normal control (NCG), hyperlipidemic control (HCG), compounds 3c-, 3d-, 3e-, 3f-, 3g- and bezafibrate (BF)-treated groups. At a dose of 15 mg/kg, compounds 3c-3g and BF (100 mg/kg) significantly (p < 0.0001) reduced elevated plasma triglycerides levels after 12 and 24 h compared to the hyperlipidemic control group. However, only compounds 3e and 3g obviously showed a significant (p < 0.0001) reduction in plasma total cholesterol levels after 12 and 24 h. Moreover, high-density lipoprotein cholesterol levels were significantly increased in all treated groups. The current study demonstrates that 5-fluoro-N-(9,10-dihydro-9,10-dioxoanthracen-8-yl)-1H-indole-2-carboxamides (3c-3g) have a definite antihyperlipidemic potential and these beneficial activities may contribute to their cardioprotective and antiatherosclerotic role.

摘要

一系列新型 5-氟-N-(9,10-二氢-9,10-二氧代蒽-8-基)-1H-吲哚-2-甲酰胺(3c-3g)被合成。本研究旨在探讨这些新型化合物对高脂血症大鼠可能的抗高血脂作用。高脂血症通过单次腹腔注射 Triton WR-1339(300 mg/kg)诱导。受试动物分为正常对照组(NCG)、高脂血症对照组(HCG)、化合物 3c-、3d-、3e-、3f-、3g-和苯扎贝特(BF)治疗组。在 15 mg/kg 剂量下,化合物 3c-3g 和 BF(100 mg/kg)在 12 和 24 小时后显著(p<0.0001)降低了升高的血浆甘油三酯水平,与高脂血症对照组相比。然而,只有化合物 3e 和 3g 在 12 和 24 小时后明显(p<0.0001)降低了血浆总胆固醇水平。此外,所有治疗组的高密度脂蛋白胆固醇水平均显著升高。本研究表明,5-氟-N-(9,10-二氢-9,10-二氧代蒽-8-基)-1H-吲哚-2-甲酰胺(3c-3g)具有明确的抗高血脂潜力,这些有益的活性可能与其心脏保护和抗动脉粥样硬化作用有关。

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