Breitbeil Fred, Kaur Navneet, Delcros Jean-Guy, Martin Bénédicte, Abboud Khalil A, Phanstiel Otto
Groupe Cycle Cellulaire, CNRS UMR 6061, IFR 97, Facult de Medecine, Universit Rennes 1, 2 Av. du Pr Leon Bernard, CS 34317, F-35043 Rennes Cedex, France.
J Med Chem. 2006 Apr 20;49(8):2407-16. doi: 10.1021/jm050814w.
Preferred conformers generated from motuporamine and anthracene-polyamine derivatives provided insight into the shapes associated with polyamine transporter (PAT) recognition and potentially dihydromotuporamine C (4a) bioactivity. Molecular modeling revealed that N(1)-(anthracen-9-ylmethyl)-3,3-triamine (6a), N(1)-(anthracen-9-ylmethyl)-4,4-triamine (6b), N(1)-(anthracen-9-ylmethyl)-N(1)-ethyl-3,3-triamine (7a), N(1)-(anthracen-9-ylmethyl)-N(1)-ethyl-4,4-triamine (7b), and 4a all preferred a hoe motif. This hoe shape was defined by the all-anti polyamine shaft extending above the relatively flat, appended ring system. The hoe geometry was also inferred by the (1)H NMR spectrum of the free amine of 7a (CDCl(3)), which showed a strong shielding effect of the anthracene ring on the chemical shifts associated with the appended polyamine chain. This shielding effect was found to be independent over a broad concentration range of 7a, which also supported an intramolecular phenomenon. The degree of substitution at the N(1)-position seems to be an important determinant of both the molecular shape preferences and biological activity of anthracenylmethyl-polyamine conjugates.
由莫土波明和蒽 - 多胺衍生物生成的优选构象体，为深入了解与多胺转运体（PAT）识别相关的形状以及潜在的二氢莫土波明C（4a）生物活性提供了线索。分子建模显示，N(1)-(蒽 - 9 - 基甲基)-3,3 - 三胺（6a）、N(1)-(蒽 - 9 - 基甲基)-4,4 - 三胺（6b）、N(1)-(蒽 - 9 - 基甲基)-N(1)-乙基 - 3,3 - 三胺（7a）、N(1)-(蒽 - 9 - 基甲基)-N(1)-乙基 - 4,4 - 三胺（7b）和4a均偏好一种锄头形状。这种锄头形状由在相对扁平的附加环系统上方延伸的全反式多胺轴定义。7a游离胺（CDCl(3)）的(1)H NMR谱也推断出了锄头几何形状，该谱显示蒽环对与附加多胺链相关的化学位移有强烈的屏蔽作用。发现这种屏蔽效应在7a的宽浓度范围内是独立的，这也支持了一种分子内现象。N(1)位的取代程度似乎是蒽基甲基 - 多胺缀合物分子形状偏好和生物活性的重要决定因素。
