Synthesis and Structure Activity Relationship of Phenolic Amides

• Main Authors: Ya-Ting Lee, 李雅婷
• Other Authors: Li-Kang Ho
• Format: Others
• Language: zh-TW
• Published: 1999
• Online Access: http://ndltd.ncl.edu.tw/handle/94569223133998080696

碩士 === 國立陽明大學 === 藥理學研究所 === 87 === Abstract Phenolic amides were identified in various plants, from families such as Solancaeae, Liliaceae, Rutaceae, Lauraceae, and Menisperimaceae. They were also found from the Chinese medicinal herbs, e.g. Dalbergia odorifera, Achyranthes bidentata, Allium chinense, and Mucuna birdwoodiana. Literature reported that phenolic amides have various biological activities such as anti-inflammatory, anti-oxidative and anti-coagulant activity effects. In this study we synthesized eighteen phenolic amides (PA01-18) with N-trans-feruloyl, N-trans-isoferuloyl or N-trans-coumaroyl acid group and dopamine derivatives; evaluated their bioactivity by D1, D2, 5-HT1A, 5-HT2, and α1 receptor binding and anti-oxidative activities methods. The results indicated: (1) For mouse cortex 5-HT1A receptor, PA10 showed the best competitive activity (IC50: 14.1+7.2μM). (2) For mouse cortex 5-HT2 receptor, PA04 showed the best competitive activity (IC50: 24.3+7.5μM). (3) For anti-oxidative activity, PA01-PA15 had better bioactivity (IC50: 2.4-8.6μM) but PA16-18 didn’t have better antioxidative activity (IC50> 20μM). The results from biological assay were analyzed by using Catalyst runs on Silicon Graphics. Catalyst/COMPARE pharmacophore which let us compare and fit hypotheses onto these molecules. HypoGen pharmacophore generates 3D hypotheses which was used to explain some of the structure activity relationships.