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

par Snoeck, Robert ;Lagneaux, Laurence ;Delforge, Alain ;Bron, Dominique ;Van Der Auwera, Philippe ;Stryckmans, Pierre ;Balzarini, Jan;de Clercq, Erik
Référence European journal of clinical microbiology & infectious diseases, 9, 8, page (615-619)
Publication Publié, 1990-08

Article révisé par les pairs

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Résumé :

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 microM, respectively, when the median-effect principle was applied. The bone marrow toxicity of zidovudine used at a low concentration (3.74 microM) was significantly decreased if the drug was combined with (S)-HPMPA, (S)-HPMPC or ganciclovir. If used at higher concentrations (74.90 microM), zidovudine showed increased myelotoxicity in the presence of (S)-HPMPA and ganciclovir, but not (S)-HPMPC.