Synthesis and biological evaluation of novel imidazole nucleosides as potential anti-dengue virus agents |
| |
| Institution: | 1. Graduate School of Pharmaceutical Science, Tokushima University, Shomachi 1-78-1, Tokushima 770-8505, Japan;2. Department of Cell Biology, Kyoto Pharmaceutical University, Misasagi-shichono-cho 1, Kyoto 607-8412, Japan;3. Department of Virology III, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashimurayama, Tokyo 208-0011, Japan;4. Department of Microbiology, Kanagawa Prefectural Institute of Public Health, 1-3-1 Shimomachiya, Chigasaki, Kanagawa 253-0087, Japan;1. Aix-Marseille Univ, CNRS UMR7258, INSERM U1068, Institut Paoli-Calmettes, CRCM, Marseille, France;2. Aix-Marseille Univ, CNRS, AFMB UMR 7257, Marseille, France;3. UMR190, Emergence des Pathologies Virales, Aix-Marseille Univ, IRD French Institute of Research for Development, EHESP French School of Public Health, 27 Boulevard Jean Moulin, Marseille, 13005, France;1. Aix-Marseille Université, AFMB (Laboratoire d’Architecture et Fonction de Macromolécules Biologiques) UMR 7257, 163 Avenue de Luminy, 13288 Marseille, France;2. CNRS, AFMB UMR 7257, 163 Avenue de Luminy, 13288 Marseille, France;1. Dipartimento di Scienze Farmaceutiche, Università degli Studi di Perugia, Via del Liceo, 1-06123 Perugia, Italy;2. Dipartimento di Bioscienze, Università di Milano, Via Celoria 26, I-20133 Milano, Italy;3. CNR-IBF, Consiglio Nazionale delle Ricerche, Istituto di Biofisica, Via Celoria 26, I-20133 Milano, Italy;4. UMR “Emergence des Pathologies Virales” (Aix-Marseille University - IRD 190 - Inserm 1207 - EHESP) & Fondation IHU Méditerranée Infection, APHM Public Hospitals of Marseille, Faculté de Médecine, 27 bd Jean Moulin, 13005 Marseille France;1. Department of Chemistry, University of Azad Jammu and Kashmir, Muzaffarabad 13100 AJK, Pakistan;2. Department of Chemistry, Quaid-i-Azam University, Islamabad 45320, Pakistan;3. Department of Chemistry and Chemical Engineering, Syed Babar Ali School of Science and Engineering, Lahore University of Management Sciences, Lahore 54792 Pakistan;4. Department of Chemistry, University of Gujrat, Gujrat 50700, Pakistan;1. Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China;2. School of Pharmacy, China Pharmaceutical University, Jiangsu, Nanjing 210009, China;3. School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China |
| |
| Abstract: | In this work, we developed imidazole nucleoside derivatives with anti-dengue virus (DENV) activity was examined. First, compounds in a nucleosides library were screened to find lead compounds which inhibit replication of DENV. As a result, 5-ethynyl-(1-β-d-ribofuranosyl)imidazole-4-carboxamide (1; EICAR) and its 4-carbonitrile derivative EICNR (2) were selected as promising antiviral compounds. However, both of them also exhibited cytotoxicity. In order to develop an effective and less toxic compound, 4′-thio and 4′-seleno derivatives of EICAR and EICNR 3–6 were prepared. The resulting 4′-thioEICAR and 4′-thioEICNR showed inhibitory effect on DENV replication without cytotoxicity as potent as ribavirin, a positive control. |
| |
| Keywords: | Imidazole nucleoside 4′-Thio-modification 4′-Seleno-modification Dengue virus Antiviral activity |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
