Anti-Herpesvirus Activities and Cytotoxicities of 2-Thiopyrimidine Nucleoside Analogues <i>in Vitro</i>
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- S Shigeta
- Department of Microbiology, School of Medicine, Fukushima Medical University, Fukushima, 960-1295, Japan
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- S Mori
- Department of Microbiology, School of Medicine, Fukushima Medical University, Fukushima, 960-1295, Japan
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- T Kira
- Department of Microbiology, School of Medicine, Fukushima Medical University, Fukushima, 960-1295, Japan
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- K Takahashi
- Department of Microbiology, School of Medicine, Fukushima Medical University, Fukushima, 960-1295, Japan
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- E Kodama
- Department of Microbiology, School of Medicine, Fukushima Medical University, Fukushima, 960-1295, Japan
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- K Konno
- Department of Microbiology, School of Medicine, Fukushima Medical University, Fukushima, 960-1295, Japan
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- T Nagata
- Tsukuba Research Laboratory, Toagosei, Tsukuba, 300-2611, Japan
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- H Kato
- Tsukuba Research Laboratory, Toagosei, Tsukuba, 300-2611, Japan
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- T Wakayama
- Tsukuba Research Laboratory, Toagosei, Tsukuba, 300-2611, Japan
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- N Koike
- Tsukuba Research Laboratory, Toagosei, Tsukuba, 300-2611, Japan
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- M Saneyoshi
- Department of Biological Sciences, Teikyo University of Science and Technology, Uenohara, Kitaturu-gun, Yamanashi, 409-0133, Japan
書誌事項
- 公開日
- 1999-08
- 権利情報
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- https://journals.sagepub.com/page/policies/text-and-data-mining-license
- http://journals.sagepub.com/page/policies/text-and-data-mining-license
- DOI
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- 10.1177/095632029901000404
- 公開者
- SAGE Publications
この論文をさがす
説明
<jats:p> Twenty 2-thiopyrimidine nucleoside analogues were synthesized and examined for inhibitory activity against herpes simplex virus (HSV) type 1 and 2, varicella-zoster virus (VZV), human cytomegalovirus (HCMV) and thymidine kinase-deficient HSV (HSV-TK) replication in vitro. 2-thiouracil (thymine) arabinoside, 2′-deoxy-2-thiouridine (or 2-thiothymidine) and their 5-halogenated derivatives showed anti-HSV activity in both RPMI8226 (human B-lymphoblastoid cells) and MRC-5 (human embryo lung cells). 2′-deoxy-5-halogenated-2-thiocytidines were also inhibitory against HSV, whereas 2-thiocytosine arabinoside and its derivatives were not inhibitory against HSV replication, except 5-bromo and 5-iodo congeners (TN-31, TN-32). Substitution of the halogen atom at the 5-position of the pyrimidine rings to an atom with a higher molecular weight increased anti-HSV and VZV activities, except for the anti-HSV activity of 2-thiouracil arabinosides. 2′-deoxy-5-methyl-, and 2′-deoxy-5-iodo-2-thiouridines (TN-17, TN-44) showed the most potent anti-HSV activity, and 2′-deoxy-5-chloro- and 2′-deoxy-5-bromo-2-thiocytidines were potent inhibitors of VZV replication. However, none of the compounds inhibited HCMV and HSV-TK<jats:sup>−</jats:sup> replication. TN-31 and TN-32 were shown to inhibited HCMV and HSV-TK<jats:sup>−</jats:sup> as well as HSV and VZV replication. The cytotoxicity of the 2-thiopyrimidine nucleoside analogues was less than that of the 2-oxy-congeners of the compounds (5-iodo-2′-deoxyuridine, 5-iodo-2′-deoxycytidine, thymine arabinoside and cytosine arabinoside). The selectivity index of 2′-deoxy-5-iodo-2-thiouridine (TN-44) was higher than that of 5-iodo-deoxyuridine. TN-17 and TN-44 were not cytotoxic to resting or stimulated human peripheral blood mononuclear cells at 400 μ, although TN-32 was cytotoxic at a concentration of 20 μ. </jats:p>
収録刊行物
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- Antiviral Chemistry and Chemotherapy
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Antiviral Chemistry and Chemotherapy 10 (4), 195-209, 1999-08
SAGE Publications
