<p>To develop novel anti-inflammatory agents, a series of new pentadienone oxime ester compounds were designed and synthesized. The structures were determined by IR, <sup>1</sup>H NMR, <sup>13 </sup>C NMR, and HRMS. All compounds have been screened for their anti-inflammatory activity by evaluating their inhibition against LPS-induced nitric oxide (NO) release in RAW 264.7 cell. Among them, compound <b>5j</b> was found to be one of the most potent compounds in inhibiting NO and IL-6 (IC<sub>50</sub> values were 6.66 µM and 5.07 µM, respectively). Preliminary mechanism studies show that title compound <b>5j</b> could significantly suppress expressions of nitric oxide synthase, COX-2, and NO, IL-6 through Toll-like receptor 4/mitogen-activated protein kinases/NF-κB signalling pathway. These data support further studies to assess rational design of more efficient pentadienone oxime ester derivatives with anti-inflammatory activity in the future.</p
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