Design, synthesis and activity of a new type of influenza virus N1 neuraminidase inhibitors.
- Author:
Fan YANG
1
;
Lei JIN
;
Nian-yu HUANG
;
Feng CHEN
;
Hua-jun LUO
;
Jian-feng CHEN
Author Information
1. Hubei Key Laboratory of Natural Products Research and Development, China Three Gorges University, Yichang 443002, China.
- Publication Type:Journal Article
- MeSH:
Antiviral Agents;
chemical synthesis;
pharmacology;
Caffeic Acids;
chemical synthesis;
pharmacology;
Cell Line, Tumor;
Drug Design;
Enzyme Inhibitors;
chemical synthesis;
pharmacology;
HEK293 Cells;
Humans;
Influenza A Virus, H5N1 Subtype;
enzymology;
Neuraminidase;
antagonists & inhibitors;
metabolism;
gamma-Aminobutyric Acid;
analogs & derivatives;
chemical synthesis;
pharmacology
- From:
Acta Pharmaceutica Sinica
2011;46(11):1344-1348
- CountryChina
- Language:Chinese
-
Abstract:
In this study, the "150-cavity", next to the H5N1 influenza virus neuraminidase activity site, has been used as the target to design and synthesize a structural analogue of chlorogenic acid, N-caffeoyl-GABA, using the flexible docking simulation. The docking study showed that the N-caffeoyl-GABA could be inserted into the "150-cavity" and combined with the Arg156 side chain by hydrogen bond. The best binding free energy of H5N1 NA-N-caffeoyl-GABA complex was -7.70 kcal mol(-1), equivalent that of the NA-oseltamivir. At the same time, using the H5N1 pseudotyping virus-based NA inhibitors screening model, we determined the inhibitory effect of oseltamivir, chlorogenic acid and N-caffeoyl-GABA on the NA. Compared with chlorogenic acid, N-caffeoyl-GABA significantly enhanced the inhibitory effect on NA, but less than oseltamivir. This study showed that the "150-cavity" could possibly be used as a new neuraminidase inhibitors target, and provided a path for the development of new neuraminidase inhibitors.
