Ruisi G, Silvestri A, Lo Guidice M T, Barbieri R, Atassi G, Huber F, Grätz K, Lamartina L
J Inorg Biochem. 1985 Dec;25(4):229-45. doi: 10.1016/0162-0134(85)80023-4.
The in vivo activity of Bu2nSnGlyGly, Na(Cl2GaGlyGly), and ClGaGlyGly (GlyGly2- = glycylglycinate) has been investigated in connection with a number of tumors. Positive results have been obtained only for the Bu2nSnIV complex in the case of leukemia P-388. In order to try to interpret the pharmacological data on a molecular basis, the nature of the species present in solutions of AlK2Sn GlyGly complexes, as well as the reactivity of aqueous Me2SnGlyGly, have been studied. The presence of chelated species (I), Figure 1, in organic solvents, and the equilibrium (I) in equilibrium (II), Figure 1, in water and mixed water-organic solvent systems, have been inferred from conductance measurements, as well as from studies by Mössbauer (in frozen solution), 1H, 13C, and 119Sn NMR, and ir spectroscopy. Moreover, solvated (II) would release AlK2SnIV moieties, as evidenced by the slow formation of (Me2SnO)n from aqueous Me2Sn GlyGly. The involvement of (I) and (II) in the transportation of these drugs across cell membranes is discussed.
已针对多种肿瘤研究了二正丁基锡甘氨酰甘氨酸（Bu2nSnGlyGly）、二氯镓钠甘氨酰甘氨酸（Na(Cl2GaGlyGly)）和二氯镓甘氨酰甘氨酸（ClGaGlyGly，GlyGly2- = 甘氨酰甘氨酸根）的体内活性。仅在白血病P - 388的情况下，二正丁基锡（IV）配合物取得了阳性结果。为了尝试从分子层面解释药理学数据，已研究了铝钾锡甘氨酰甘氨酸配合物溶液中存在的物种的性质，以及二甲基锡甘氨酰甘氨酸在水溶液中的反应活性。通过电导测量以及穆斯堡尔谱（在冷冻溶液中）、1H、13C和119Sn核磁共振以及红外光谱研究，推断出在有机溶剂中存在螯合物种（I，图1），以及在水和水 - 有机溶剂混合体系中存在平衡（I）处于平衡（II）（图1）。此外，溶剂化的（II）会释放出铝钾锡（IV）部分，从二甲基锡甘氨酰甘氨酸水溶液中缓慢形成（Me2SnO）n即可证明。讨论了（I）和（II）在这些药物跨细胞膜转运中的作用。
