The cytostatic effects and mechanism of action of antiviral acyclic adenine nucleotide analogs in L1210 mouse leukemia cells.

The growth and DNA synthesis of mouse leukemic cells L1210 in vitro was inhibited by (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine (HPMPA) by 50% at concentrations of 57.0 and 185.0 mumols/l, respectively, 9-(2-Phosphonylmethoxyethyl)adenine (PMEA) inhibited the cell growth and DNA synthesis at concentrations of 15.5 and 250.0 mumols/l. The 2-amino congeners of the above analogs were still more efficient: The corresponding values for 2-amino-PMEA were 6.0 and 10.0 mumols/l, and for 2-amino-HPMPA 19.5 and 50.0 mumols/l, respectively. The results suggest that probably at least a part of the growth inhibitory action of PMEA is due to mechanisms not related to its interference with the DNA synthesis.