College of Pharmaceutical Sciences, Capital Medical University, No 10 You An Men Xitoutiao, Beijing 100069, PR China.
Eur J Med Chem. 2011 Nov;46(11):5598-608. doi: 10.1016/j.ejmech.2011.09.027. Epub 2011 Sep 24.
High anti-thrombotic activity of aminoacid modified tetrahydro-β-carbolines was generally correlated with a small proximity of the side chain of the aminoacid residue to the carboline-cycle. This paper explored that the aromatization of the tetrahydro-β-carboline-cycle of N-(1-methyl-β-tetrahydrocarboline-3-carbonyl)-N'-(aminoacid-acyl)-hydrazines leaded to N-(1-methyl-β-carboline-3-carbonyl)-N'-(aminoacid-acyl)-hydrazines and decreased the proximity of the side chain of the aminoacid residue to the carboline-cycle. The in vitro activities of inhibiting pig platelet aggregation induced by PAF, ADP, and AA, as well as the in vivo anti-thrombotic activities of inhibiting rat thrombosis of these aromatized derivatives were generally higher than that of N-(1-methyl-β-tetrahydrocarboline-3-carbonyl)-N'-(aminoacid-acyl)-hydrazines. The understanding was also obtained from the 3D QSAR analysis.
高抗血栓活性的氨基酸修饰四氢-β-咔啉通常与氨基酸残基的侧链与咔啉环的接近程度有关。本文探讨了 N-(1-甲基-β-四氢咔啉-3-羰基)-N'-(氨基酸酰基)-酰肼的四氢-β-咔啉环的芳构化导致 N-(1-甲基-β-咔啉-3-羰基)-N'-(氨基酸酰基)-酰肼的形成，从而降低了氨基酸残基的侧链与咔啉环的接近程度。这些芳构化衍生物抑制 PAF、ADP 和 AA 诱导的猪血小板聚集的体外活性以及抑制大鼠血栓形成的体内抗血栓活性通常高于 N-(1-甲基-β-四氢咔啉-3-羰基)-N'-(氨基酸酰基)-酰肼。通过 3D-QSAR 分析也得到了这一认识。
