Isobutylhydroxyamides from Zanthoxylum bungeanum and Their Suppression of NO Production

Abstract

Four new unsaturated aliphatic acid amides, named zanthoamides A-D (<b>1</b>-<b>4</b>), and eight known ones-tetrahydrobungeanool (<b>5</b>), ZP-amide A (<b>6</b>), ZP-amide B (<b>7</b>), ZP-amide C (<b>8</b>), ZP-amide D (<b>9</b>), ZP-amide E (<b>10</b>), bugeanumamide A (<b>11</b>), and (2<i>E</i>,7<i>E</i>,9<i>E</i>)-<i>N</i>-(2-hydroxy-2-methylpropyl)-6,11-dioxo-2,7,9-dodecatrienamide (<b>12</b>)-were isolated from the pericarps of <i>Zanthoxylum bungeanum</i>. The structures of these compounds were elucidated by extensive use of spectroscopic methods, including HRESIMS, 1D and 2D NMR analyses and comparison with previously reported data. Compound <b>4</b> contained a rare C₆ fatty acid unit with an acetal group. Results revealed that compounds <b>1</b>, <b>5</b>, <b>6</b>, and <b>12</b> showed inhibitory effects on nitric oxide (NO) production in LPS-stimulated RAW 264.7 macrophages, with IC₅₀values of 48.7 ± 0.32, 27.1 ± 1.15, 49.8 ± 0.38, and 39.4 ± 0.63 µM, respectively, while the other compounds were inactive (IC₅₀ > 60 μM). They could contribute to the anti-inflammatory effects of <i>Z. bungeanum</i> by suppression of NO production.