1-β-D-Arabinofuranosyl-2-amino-1,4(2H)-4-iminopyrimidine (ara-AlPy) and its 3'-phosphate (ara-AIPyP) have been synthesized and have been shown to be very effective in the treatment of leukemia L1210 in female C57BL/6 x DBA/2 (hereafter known as BDF1) mice (ara-AIPy increased life span 222% and cured 21 of 30 animals, ara-AIPyp increased life span 145% and cured 2 of 6 animals). The antileukemic activity of ara-AIPy is comparable to that of anhydro-ara-C. ara-AIPyP was also effective (i.p. treatments) against intracerebrally implanted leukemia L1210 in female BDF1 mice (increased life span 126%, cured 1 of 6 animals), ara-AIPyp was not active against a leukemia L1210 strain which was resistant to ara-C treatments. ara-AIPy and ara-AIPyP were not substrates for enzymic deamination by crude extracts of Escherichia coli. ara-AIPyP was a substrate for E. coli alkaline phosphatase. In a Tris-HCl buffer (pH 7.4, 37°) ara-AIPy hydrolyzed to provide 2,2'-anhydro-1-β-D-arabinofuranosylcytosine and 1-β-D-arabinofuranosylcytosine (ara-C). Most of the ara-C produced by hydrolysis of ara-AIPy over a 24-hr period was due to direct deamination of ara-AIPy. Some ara-C (<10%) was also produced due to the hydrolysis of 2,2'-anhydro-1-β-D-arabinofuranosylcytosine. Under identical conditions of hydrolysis, ara-AIPyP gave 2-2'-anhydro-β-D-arabinofuranosylcytosine 3'-phosphate and 1-β-D-arabinofuranosylcytosine 3'-phosphate. Studies illustrate that ara-AIPy and ara-AIPyP are new deaminase-resistant depot forms of ara-C.
|Original language||English (US)|
|Number of pages||5|
|State||Published - Aug 1979|
ASJC Scopus subject areas
- Cancer Research