| 摘要 |
<p>Pyrrolo[1,2-α]benzimidazoles having structural formulae (A), (B) and (C) were prepared as reductive alkylating agents of DNA. In these compounds only the reduced (hydroquinone) form acts as the alkylating agent. DT-diaphorase is the prerequisite two-electron reducing enzyme which carries out the activation process. Depending on the cancer cell line organ and species source, the substrate and inhibition properties of the enzyme can vary widely. Therefore the design of the yujungamycins was to take advantage of subtle differences in the enzyme structure among cancer cell lines. In doing so, cancer- cell- selective drugs were designed possessing outstanding in vivo activity. The 3-substituent influences the reductive activation process and the substituents (amino, acetamido, and carbamido) were placed at this position with varying configuration (R and S). The variation in hydrogen bonding and stereochemistry permits the yujungamycins to recognize DT-diaphorase from select cancer cells resulting in a 'magic bullet' directed toward such cells.</p> |
