Finch R A, Vasquez K M, Hanna N B, Revankar G R, Robins R K, Avery T L
ICN Nucleic Acid Research Institute, Costa Mesa, CA 92626.
Cancer Lett. 1990 Apr 9;50(1):63-70. doi: 10.1016/0304-3835(90)90180-6.
Preclinical investigations in vivo revealed unexpected differences in the biological characteristics of 2-amino-9-beta-D-ribofuranosylpurine-6-sulfenamide (sulfenosine, 1) and 2-amino-9-beta-D-ribofuranosylpurine-6-sulfonamide (sulfonosine, 2), two novel but structurally related derivatives of 6-thioguanosine (6TGR). Strikingly, the addition of a fully oxidized sulfur atom at the 6 position of sulfenosine produced a purine derivative (sulfonosine) that was remarkably active against experimental leukemia resistant to treatment with either sulfenosine or 6TGR. This slight structural modification also appeared to influence solubility, scheduling capability, and oral activity as well as penetration of the central nervous system (CNS) and the onset of cellular resistance. These findings underscore the dramatic changes in biologic activity that can be produced by subtle modifications in molecular structure. We trust they may also contribute to the development of improved clinical therapy.
体内临床前研究揭示了2-氨基-9-β-D-呋喃核糖基嘌呤-6-亚磺酰胺（亚磺腺苷，1）和2-氨基-9-β-D-呋喃核糖基嘌呤-6-磺酰胺（磺腺苷，2）这两种6-硫鸟苷（6TGR）的新型但结构相关的衍生物在生物学特性上存在意想不到的差异。引人注目的是，在亚磺腺苷的6位添加一个完全氧化的硫原子产生了一种嘌呤衍生物（磺腺苷），该衍生物对用亚磺腺苷或6TGR治疗耐药的实验性白血病具有显著活性。这种微小的结构修饰似乎还影响了溶解度、给药方案能力、口服活性以及中枢神经系统（CNS）的渗透和细胞耐药性的产生。这些发现强调了分子结构的细微修饰可导致生物活性发生巨大变化。我们相信它们也可能有助于改进临床治疗的发展。
