Design and synthesis of pinanamine derivatives as anti-influenza A M2 ion channel inhibitors
| Autor: | Matthew R. Rosenberg, Marco G. Casarotto, Junting Wan, Zhiyuan Li, Wei Cui, Zhengchao Tu, Wenhui Hu, Yanling Jie, Yiping Xiao, Shaogao Zeng, Xin Zhao |
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| Rok vydání: | 2012 |
| Předmět: |
Rimantadine
Mutant Microbial Sensitivity Tests Viral Plaque Assay Pharmacology Biology medicine.disease_cause Antiviral Agents Ion Channels Cell Line Viral Matrix Proteins chemistry.chemical_compound Virology medicine Influenza A virus Animals Humans Imidazole Ion channel Molecular Structure Wild type Amantadine chemistry Cell culture medicine.drug |
| Zdroj: | Antiviral Research. 96:91-99 |
| ISSN: | 0166-3542 |
| Popis: | The adamantanes are a class of anti-influenza drugs that inhibit the M2 ion channel of the influenza A virus. However recently, the clinical effectiveness of these drugs has been called into question due to the emergence of adamantane-insensitive A/M2 mutants. Although we previously reported (1R,2R,3R,5S)-3-pinanamine 3 as a novel inhibitor of the wild type influenza A virus M2 protein (WT A/M2), limited inhibition was found for adamantane-resistant M2 mutants. In this study, we explored whether newly synthesized pinanamine derivatives were capable of inhibiting WT A/M2 and selected adamantane-resistant M2 mutants. Several imidazole and guanazole derivatives of pinanamine were found to inhibit WT A/M2 to a comparable degree as amantadine and one of these compounds 12 exhibits weak inhibition of A/M2-S31N mutant and it is marginally more effective in inhibiting S31NM2 than amantadine. This study provides a new insight into the structural nature of drugs required to inhibit WT A/M2 and its mutants. |
| Databáze: | OpenAIRE |
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