tetano
Editor, Senior Moderator
Antiviral Res. 2012 Sep 12. pii: S0166-3542(12)00198-2. doi: 10.1016/j.antiviral.2012.09.001. [Epub ahead of print]
Design and Synthesis of Pinanamine Derivatives as Anti-Influenza A M2 Ion Channel Inhibitors.
Zhao X, Jie Y, Rosenberg MR, Wan J, Zeng S, Cui W, Xiao Y, Li Z, Tu Z, Casarotto MG, Hu W.
Source
Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, Guangdong 510530, People's Republic of China.
Abstract
The adamatanes 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 S31N M2 than amantadine. This study provides a new insight into the structural nature of drugs required to inhibit WT A/M2 and its mutants.
Copyright ? 2012. Published by Elsevier B.V.
PMID:
22982118
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/22982118
Design and Synthesis of Pinanamine Derivatives as Anti-Influenza A M2 Ion Channel Inhibitors.
Zhao X, Jie Y, Rosenberg MR, Wan J, Zeng S, Cui W, Xiao Y, Li Z, Tu Z, Casarotto MG, Hu W.
Source
Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, Guangdong 510530, People's Republic of China.
Abstract
The adamatanes 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 S31N M2 than amantadine. This study provides a new insight into the structural nature of drugs required to inhibit WT A/M2 and its mutants.
Copyright ? 2012. Published by Elsevier B.V.
PMID:
22982118
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/22982118