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Heterodimers of Histidine and Amantadine as Inhibitors for Wild Type and Mutant M2 Channels of Influenza A
Author(s) -
Zhang Wenjuan,
Xu Jing,
Liu Fang,
Li Chufang,
Jie Yanling,
Chen Shaopeng,
Li Zhiyuan,
Liu Jinsong,
Chen Ling,
Zhou Guochun
Publication year - 2010
Publication title -
chinese journal of chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.28
H-Index - 41
eISSN - 1614-7065
pISSN - 1001-604X
DOI - 10.1002/cjoc.201090242
Subject(s) - chemistry , amantadine , adamantane , mutant , histidine , imidazole , stereochemistry , amine gas treating , rimantadine , influenza a virus , biochemistry , enzyme , pharmacology , virus , virology , organic chemistry , gene , medicine , biology
Inhibitors bearing the imidazole, adamantane and related structures were synthesized and tested against WT, S31N and S31N‐L26I mutant M2 channels. Although amantadine ( 1 ) only inhibited WT M2 channel, compound 6 containing the imidazole and adamantane groups showed good inhibitory activity to WT and mutant M2 channels. The stereochemistry and basic p K a of α ‐amine are important for the activity of inhibitors and our data showed that derivatives of natural histidine are more active for M2 channels than those of unnatural histidine. The significance of our present results is that we have established a prospective strategy of drug discovery of WT and mutant M2 channels against influenza A.