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外文期刊>british journal of haematology
>Comparison of benzimidazole nucleosides and ganciclovir on thein vitroproliferation and colony formation of human bone marrow progenitor cells
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Comparison of benzimidazole nucleosides and ganciclovir on thein vitroproliferation and colony formation of human bone marrow progenitor cells
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机译：Comparison of benzimidazole nucleosides and ganciclovir on thein vitroproliferation and colony formation of human bone marrow progenitor cells
Recently we have shown that certain benzimidazole ribonucleosides are potent and selective inhibitors of human cytomegalovirus (HCMV) replication. Because antiviral drugs used to treat HCMV and human immunodeficiency virus (HIV) infections can suppress marrow progenitors, we have evaluated the most promising of the new benzimidazoles for their effects on human bone marrow cellsin vitro. In an initial study of the bone marrow toxicity of one of the most active compounds, 100 μm2‐bromo‐5,6‐dichloro‐1‐(β‐d‐ribofuranosyl)‐benzimidazole (BDCRB) inhibited cell proliferation by 20 over a 10 d period compared to 52 inhibition by 100 μmganciclovir, the drug currently most used to treat HCMV infections. The effects of these drugs and selected other benzimidazole nucleosides were evaluated more extensively in haemopoietic progenitor cell colony formation assays. Colony formation was determined at 2 weeks and scored as either burst forming units‐erythroid (BFU‐E), or colony forming units‐granulocyte/macrophage (CFU‐GM). At the highest concentration tested, 100 μmBDCRB only moderately affected BFU‐E or CFU‐GM formation (31 and 47 inhibition, respectively). This concentration is 10‐fold higher than that required to produce a 10 000‐fold reduction in virus titre. Evaluation of the 2‐chloro analog of BDCRB (TCRB) which is less potent against HCMV, its 5′‐deoxy analog (5′‐dTCRB) which is more potent, and the 2‐unsubstituted compound (DRB) gave the following order of haemopoietic toxicity: DRB TCRB≥ 5′‐dTCRB BDCRB. In contrast to the benzimidazoles, ganciclovir decreased colony formation by 84 for BFU‐E and 86 for CFU‐GM at 100 μm. These results establish that certain benzimidazole nucleosides are less toxic to haemopoietic progenitors than the preferred drug now being used clinically for HCMV infections. The results also establish that different structure–activity relationships exist for antiviral activity and progenitor cell toxicity, thereby s
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