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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