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J Bacteriol Virol. 2016 Dec;46(4):239-247. English. Original Article.
Jeong JJ , Lee YS , Kim DH .
Department of Life and Nanopharmaceutical Sciences, College of Pharmacy, Kyung Hee University, Seoul, Korea.

In the previous study, we found that flavonoids and ginsenosides exhibited high eliminate rates of human immunodeficiency virus type 1 (HIV-1) D3-transfected macrophages. Based on these findings, here we synthesized the derivatives of gallic acid, including methyl gallate, methyl 4-O-methyl gallate, methyl 3,4-O-dimethyl gallate, and methyl 3,4,5-O-trimethyl gallate and measured their cellular toxic effects against HIV-1-infected macrophages. Of these, treatment with methyl 4-O-methyl gallate in the presence of lipopolysaccharide (LPS) and cycloheximide (CHX) most effectively eliminated HIV-1-transfected cytoprotective human microglial CHME5 cells and HIV-1-D3-infected human primary macrophages. Furthermore, these strongly inhibited LPS/CHX-induced phosphorylation of phosphoinositide 3-kinase (PI3K), pyruvate dehydrogenase lipoamide kinase isozyme 1 (PDK1), Akt, and glycogen synthase kinase-3β (GSK-3β) in the Tat-transfected cells and HIV-1-D3-infected human primary macrophages. These findings suggest that methyl 4-O-methyl gallate may be a promising candidate for eliminating HIV-1 infected macrophages by blocking PI3K/Akt signaling pathway.

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