Inhibitory effects of potent inhibitors of human immunodeficiency virus and cytomegalovirus on the growth of human granulocyte-macrophage progenitor cells in vitro

Abstract

Phosphonoformate, ganciclovir, zidovudine and the novel acyclic nucleotide analogues (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine [(S)-HPMPA] and (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine [(S)-HPMPC] were evaluated for their inhibitory effect on colony forming unit formation by human granulocyte-macrophage progenitor cells (obtained from 11 healthy volunteers) in vitro. The 50 % inhibitory dose of zidovudine, (S)-HPMPA, (S)-HPMPC, ganciclovir and phosphonoformate were 10.61, 16.55, 80.88, 41.02 and 668.64 µM, respectively, when the median-effect principle was applied. The bone marrow toxicity of zidovudine used at a low concentration (3.74 µM) was significantly decreased if the drug was combined with (S)-HPMPA, (S)-HPMPC or ganciclovir. If used at higher concentrations (74.90 µM), zidovudine showed increased myelotoxicity in the presence of (S)-HPMPA and ganciclovir, but not (S)-HPMPC.