Syntheses of Ethyl Pyruvate’s Bioisosteres Inhibiting Inducible Nitric Oxide Production in Lipopolysaccharide-induced BV2 Cells

Author(s): Ju-Young Park, Byung-Wook Kim, Soon-Jung Kwon, Dong-Kug Choi, Ja-Kyeong Lee, Sung-Hwa Yoon

Journal Name: Letters in Drug Design & Discovery

Volume 12 , Issue 7 , 2015

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Graphical Abstract:


Various bioisosteres of ethyl pyruvate (EP), where the oxygen atom in the ethoxy group was replaced by the corresponding bioisosteric atom such as carbon, nitrogen, and sulfur atoms, were synthesized and their inhibitory effects were tested for nitric oxide (NO) production and inducible NO synthase (iNOS) expression in lipopolysaccharide (LPS)-induced BV2 cells. The synthesized compounds generally revealed better activity than EP. Especially, the thio-bioisostere 4c (IC50 = 3.6 µM) exhibited a potency about 4.5 times greater than that of EP (IC50 = 16.1 µM) and suppressed NO production dose-dependently without cytotoxicity. Compound 4c also inhibited iNOS expression in LPS-induced BV2 cells at 1 µM and 10 µM concentrations. These results suggested that the ethoxy group in EP is not essential for the suppression of NO production and that 4c has potential as a potent inhibitor of NO production.

Keywords: Ethyl pyruvate, bioisosteres, microglia, BV2 cell, nitric oxide, inhibitor.

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Article Details

Year: 2015
Page: [591 - 596]
Pages: 6
DOI: 10.2174/1570180812999150225112225
Price: $65

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