دورية أكاديمية
In vitro and in vivo anti-picornavirus activity of some p-benzoylphenoxypyridines.
| العنوان: | In vitro and in vivo anti-picornavirus activity of some p-benzoylphenoxypyridines. |
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| المؤلفون: | Kenny MT, Dulworth JK, Torney HL |
| المصدر: | Antiviral research [Antiviral Res] 1986 Oct; Vol. 6 (6), pp. 355-67. |
| نوع المنشور: | Comparative Study; Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: Netherlands NLM ID: 8109699 Publication Model: Print Cited Medium: Print ISSN: 0166-3542 (Print) Linking ISSN: 01663542 NLM ISO Abbreviation: Antiviral Res Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Amsterdam : Elsevier Original Publication: [Amsterdam ; New York : Elsevier/North-Holland Biomedical Press, c1981- |
| مواضيع طبية MeSH: | Antiviral Agents/*pharmacology , Picornaviridae/*drug effects , Pyridines/*pharmacology, Animals ; Drug Evaluation, Preclinical/methods ; Echovirus 6, Human/drug effects ; Enterovirus/drug effects ; Enterovirus B, Human/drug effects ; HeLa Cells/cytology ; HeLa Cells/drug effects ; Humans ; Mice ; Pyridines/therapeutic use ; Pyridines/toxicity ; Structure-Activity Relationship |
| مستخلص: | Fifteen p-benzoylphenoxypyridines were initially evaluated for their in vitro activity against rhinoviruses (RV) 1A, 2 and 64 and coxsackie virus (Cox) A21 and for their oral prophylactic and therapeutic activity in Swiss albino mice lethally challenged with Cox A21. One compound, (4-[(5-methylsulfonyl-2-pyridinyl)oxy]phenyl) phenyl methanone, was selected for additional evaluation. These studies showed the compound to possess MIC50 values of less than or equal to 5 micrograms/ml against only 6 of 20 (30.0%) RV serotypes tested. In contrast, the compound was active at concentrations of less than or equal to 5.0 micrograms/ml against 10 of 12 (83.3%) enteroviruses evaluated. In vivo studies showed the compound to significantly protect mice lethally infected with Cox A21 after a single oral dose of 37.5 mg/kg (P less than 0.02) and during a regimen of continuous oral doses of at least 4.7 mg/kg per day (P less than 0.001). Mechanism of action studies indicated that the compound inhibits picornavirus uncoating or some earlier virus-host cell-associated event. Isotopic studies show that (4-[(5-methylsulfonyl-2-pyridinyl)oxy]phenyl) phenyl methanone perturbs HeLa cell macromolecular synthesis at concentrations of as low as 3.12 micrograms/ml. This concentration is only 4-fold higher than the concentration of compound necessary to inhibit Cox A21 RNA synthesis by 90%. This narrow therapeutic ratio limits the potential clinical utility of this compound to all but the most serious picornavirus infections. |
| المشرفين على المادة: | 0 (Antiviral Agents) 0 (Pyridines) |
| تواريخ الأحداث: | Date Created: 19861001 Date Completed: 19861215 Latest Revision: 20190919 |
| رمز التحديث: | 20221208 |
| DOI: | 10.1016/0166-3542(86)90017-3 |
| PMID: | 3777916 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 0166-3542 |
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| DOI: | 10.1016/0166-3542(86)90017-3 |