Synthesis of 1,N6-etheno-2-aza-adenosine (2-aza-epsilon-adenosine): a new cytotoxic fluorescent nucleoside.
1,N(6)-Etheno-2-aza-adenosine was synthesized by treating 1,N(6)-etheno-adenosine with alkali, followed by nitrosation. The mechanism of formation of this novel nucleoside was elucidated using adenosine tritiated at C-8 and C-2, and was found to deformylate exclusively at C-2. This new 2-aza nucleoside fluoresces at 494 nm when excited at 358 nm. Toxicity study showed the compound is active in a rat mammary tumor tissue culture line, but inactive in HeLa and Glioma 26 tissue culture lines. It was also found to selectively inhibit the thymidine incorporation into DNA in a rat mammary tumor, but exhibits no ill effect on normal proliferative tissue. The reactive intermediate 3-beta-D-ribofuranosyl-4-amino-5-(imidazol-2-yl) imidazole was identified and was found to be an active agent in tissue culture.
Tsou
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KC
Yip
K F
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Miller
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EE
Lo
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KW
D000241:Adenosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000627:therapeutic use; D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000627:therapeutic use; D005260:Female; D005456:Fluorescent Dyes / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy / Q000378:metabolism; D051381:Rats; D013050:Spectrometry, Fluorescence; D014018:Tissue Distribution
C407765:1,N(6)-etheno-2-aza-adenosine; D018906:Antineoplastic Agents, Alkylating; D005456:Fluorescent Dyes; D000241:Adenosine