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Structure and biological properties of 2H-1-benzopyran-2-one (coumarin) derivatives
Pharmaceutical Chemistry Journal ( IF 0.8 ) Pub Date : 2006-11-01 , DOI: 10.1007/s11094-006-0203-7 A. Z. Abyshev , V. A. Gindin , E. V. Semenov , E. M. Agaev , A. A. Abdulla-zade , A. B. Guseinov
Pharmaceutical Chemistry Journal ( IF 0.8 ) Pub Date : 2006-11-01 , DOI: 10.1007/s11094-006-0203-7 A. Z. Abyshev , V. A. Gindin , E. V. Semenov , E. M. Agaev , A. A. Abdulla-zade , A. B. Guseinov
The physicochemical and pharmacological properties of some natural derivatives of 2H-1-benzopyran-2-one (coumarin) have been studied, including decursinol and obtusifol, which are the most promising compounds for practical applications. Using high-resolution 1H and 13C NMR spectra in comparison to the published data, the structure of obtusifol is finally established. Decursinol exhibited the most pronounced antiarrhythmic activity on the model of calcium-chloride-induced arrhythmia in rats: in a doze of 0.5 mg-kg, this compound prevented the loss of experimental animals and restored the sinusoidal rhythm in 100% of cases. The therapeutic antiarrhythmic index (AI = LD50/ED50) of decursinol (AI = 470) significantly exceeds the values for well-known drugs such as quinidine, novocainamide, and lidocaine (AI = 16.5, 17.0 and 22.2, respectively). The antiarrhythmic activity of campestrinol and obtusifol was close to that of decursinol. It was found that obtusifol, decursinol, diumancal, and their analogs (representing calcium ion antagonists of the new generation) significantly influence the potential-dependent conductivity of calcium channels not only of the L-type (encountered in muscles, heart and vessels), but also of the N-and T-types, most widely distributed in the central nervous system and ganglion.
中文翻译:
2H-1-benzopyran-2-one(香豆素)衍生物的结构和生物学特性
已经研究了 2H-1-benzopyran-2-one(香豆素)的一些天然衍生物的理化和药理特性,包括 decursinol 和 obtusifol,它们是最有前途的实际应用化合物。使用高分辨率 1H 和 13C NMR 谱与已发表的数据进行比较,最终确定了钝叶酚的结构。在氯化钙诱导的大鼠心律失常模型中,Decursinol 表现出最显着的抗心律失常活性:在 0.5 mg-kg 的瞌睡中,该化合物可防止实验动物的损失并在 100% 的情况下恢复正弦节律。decursinol (AI = 470) 的治疗性抗心律失常指数 (AI = LD50/ED50) 显着超过了奎尼丁、诺卡因胺和利多卡因等知名药物的值(AI 分别为 16.5、17.0 和 22.2)。菜油雌酚和钝叶酚的抗心律失常活性与十香酚接近。研究发现,钝化酚、十香酚、地黄酮及其类似物(代表新一代钙离子拮抗剂)不仅对 L 型(在肌肉、心脏和血管中遇到),还显着影响钙通道的电位依赖性电导率,但也属于 N 型和 T 型,最广泛分布于中枢神经系统和神经节。
更新日期:2006-11-01
中文翻译:
2H-1-benzopyran-2-one(香豆素)衍生物的结构和生物学特性
已经研究了 2H-1-benzopyran-2-one(香豆素)的一些天然衍生物的理化和药理特性,包括 decursinol 和 obtusifol,它们是最有前途的实际应用化合物。使用高分辨率 1H 和 13C NMR 谱与已发表的数据进行比较,最终确定了钝叶酚的结构。在氯化钙诱导的大鼠心律失常模型中,Decursinol 表现出最显着的抗心律失常活性:在 0.5 mg-kg 的瞌睡中,该化合物可防止实验动物的损失并在 100% 的情况下恢复正弦节律。decursinol (AI = 470) 的治疗性抗心律失常指数 (AI = LD50/ED50) 显着超过了奎尼丁、诺卡因胺和利多卡因等知名药物的值(AI 分别为 16.5、17.0 和 22.2)。菜油雌酚和钝叶酚的抗心律失常活性与十香酚接近。研究发现,钝化酚、十香酚、地黄酮及其类似物(代表新一代钙离子拮抗剂)不仅对 L 型(在肌肉、心脏和血管中遇到),还显着影响钙通道的电位依赖性电导率,但也属于 N 型和 T 型,最广泛分布于中枢神经系统和神经节。