Syntheses of triazole-modified zanamivir analogues via click chemistry and anti-AIV activities.
Sixteen novel 4-triazole-modified zanamivir (1) analogues were synthesized using the click reactions, and their inhibitory activities against avian influenza virus (AIV, H5N1) were determined. Compound 3b exerts promising inhibitory activity with EC(50) of 6.4 microM, which is very close to that of zanamivir (EC(50) = 2.8 microM). Molecular modeling provided the information about the binding model between inhibitors and neuraminidase, which are in good agreement with inhibitory activities.
Li
Jian
J
Drug Discovery and Design Centre, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 201203, China.
Zheng
Mingyue
M
Tang
Wei
W
He
Pei-Lan
PL
Zhu
Weiliang
W
Li
Tianxian
T
Zuo
Jian-Ping
JP
Liu
Hong
H
Jiang
Hualiang
H
D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism; D006146:Guanidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000187:drug effects*; D007251:Influenza, Human / Q000517:prevention & control; D008958:Models, Molecular; D009439:Neuraminidase / Q000037:antagonists & inhibitors / Q000378:metabolism; D011714:Pyrans / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D012794:Sialic Acids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014230:Triazoles; D053243:Zanamivir
D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D006146:Guanidines; D011714:Pyrans; D012794:Sialic Acids; D014230:Triazoles; D009439:Neuraminidase; D053243:Zanamivir