Abstract
Preclinical investigations in vivo revealed unexpected differences in the biological characteristics of 2-amino-9-β-d-ribofuranosylpurine-6-sulfenamide (sulfenosine, 1) and 2-amino-9-β-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.
Original language | English (US) |
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Pages (from-to) | 63-70 |
Number of pages | 8 |
Journal | Cancer Letters |
Volume | 50 |
Issue number | 1 |
DOIs | |
State | Published - Apr 9 1990 |
Externally published | Yes |
Keywords
- blood-brain barrier
- chemotherapeutic characterization
- derivatives of 6-thioguanosine
- experimental leukemia
- resistance
ASJC Scopus subject areas
- Oncology
- Cancer Research