oleanane and Inflammation

We report the synthesis and biological activity of C-24 demethyl CDDO-Me 2 and the C-28 amide derivatives 3 and 4, which are analogues of the anti-inflammatory synthetic triterpenoid bardoxolone methyl (CDDO-Me) 1. Demethylation of the C-24 methyl group was accomplished via "abnormal Beckmann" rearrangement and subsequent ring A reformation. Amides 3 and 4 were found to be potent inhibitors of the production of the inflammatory mediator NO in vitro.

Topics: Animals; Anti-Inflammatory Agents; Drug Design; Female; Inflammation; Mice; Molecular Conformation; Nitric Oxide; Oleanolic Acid; RAW 264.7 Cells

Five oleanane-type saponins, 3-O-β-D-glucuronopyranosylzanhic acid 28-O-β-D-xylopyranosyl-(1→3)-[α-L-rhamnopyranosyl-(1→2)]-(4-O-acetyl)-β-D-fucopyranosyl ester (1), 3-O-β-D-glucopyranosylzanhic acid 28-O-β-D-xylopyranosyl-(1→3)-[α-L-rhamnopyranosyl-(1→2)]-(4-O-acetyl)-β-D-fucopyranosyl ester (2), zanhic acid 28-O-β-D-xylopyranosyl-(1→3)-[α-L-rhamnopyranosyl-(1→2)]-(4-O-acetyl)-β-D-fucopyranosyl ester (3), zanhic acid 28-O-α-L-rhamnopyranosyl-(1→2)-4-O-[(3'-hydroxy-2'-methyl-butyroyloxy)-3-hydroxy-2-methyl-butyroyloxy]-β-D-fucopyranosyl ester (4), medicagenic acid 28-O-α-L-rhamnopyranosyl-(1→2)-4-O-[(3'-hydroxy-2'-methyl-butyroyloxy)-3-hydroxy-2-methyl-butyroyloxy]-β-D-fucopyranosyl ester (5), were isolated from the root barks of Ganophyllum giganteum. Compounds 4 and 5 possessed an unusual substitution of the C-4 position of the β-D-fucopyranosyl moiety by a C10 ester group formed by two symmetrical C5 nilic acid. From a chemotaxonomic point of view, their structures are in accordance with the previous saponins isolated from the Doratoxyleae tribe of the Sapindaceae family. Their cytotoxicity and anti-inflammatory activity were also evaluated.

Topics: Acylation; Animals; Anti-Inflammatory Agents, Non-Steroidal; Antineoplastic Agents, Phytogenic; Biological Products; Cell Line, Tumor; Cell Proliferation; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Humans; Hydrolysis; Inflammation; Mice; Molecular Conformation; Oleanolic Acid; Plant Roots; Sapindaceae; Saponins; Structure-Activity Relationship