Synthesis,anti-inflammatory activity and modeling studies of cycloartane-type terpenes derivatives isolated from Parthenium argentatum |
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Institution: | 1. Pharmacokinetics and Bioanalysis Center, Shin Nippon Biomedical Laboratories, Ltd., Kainan, Japan;2. Drug Safety Research Center, Shin Nippon Biomedical Laboratories, Ltd., Kagoshima, Japan;3. Laboratory of Drug Metabolism and Pharmacokinetics, Showa Pharmaceutical University, Machida, Japan |
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Abstract: | The 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced edema model in mice determined the anti-inflammatory activities in vivo of argentatins A, B and D, the main cycloartenol-type triterpenes present in Parthenium argentatum. Our results showed that argentatin B (ED50 = 1.5 × 10?4 mmol/ear) and argentatin A (ED50 = 2.8 × 10?4 mmol/ear) were more potent anti-inflammatory agents than indomethacin (ED50 = 4.5 × 10?4 mmol/ear), the reference drug. Based on these findings, we decided to evaluate 13 derivatives of argentatins A and B. All the derivatives showed anti-inflammatory activity in the TPA-induced edema model in mice. The most active compound was 25-nor-cycloart-3, 16-dione-17-en-24-oic acid, obtained from argentatin A (ED50 = 1.4 × 10?4 mmol/ear). Argentatin B was assayed as inhibitor of COX-2 activity one of the key enzymes involved in the TPA assay. The results showed that argentatin B at 15 μM doses inhibited 77% COX-2 activity. Docking studies suggest that argentatin B interacts with Arg 120, a key residue for COX-2 activity. |
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Keywords: | Argentatins Triterpenes Cycloartanes Anti-inflammatory activity TPA-induced mice model Docking |
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