Müller K, Breu K
Institut für Pharmazeutische Chemie, Westfälische Wilhelms-Universität Münster, Germany.
Arch Pharm (Weinheim). 1999 Jan;332(1):31-5. doi: 10.1002/(sici)1521-4184(19991)332:1<31::aid-ardp31>3.0.co;2-t.
1,8-Dihydroxy-9(10H)-anthracenones with a 10-alpha-aminoacyl group were synthesized using either a mixed-anhydride coupling method or Boc-protected oxazolidinediones. The novel anthracenones were evaluated as inhibitors of the biosynthesis of 12(S)-hydroxyeicosatetraenoic acid (12(S)-HETE) in epidermal homogenate of mice and for inhibition of the growth of HaCaT keratinocytes. These cells were also tested for their susceptibility for the action of the most potent members of this series on plasma membrane integrity, in order to confirm that inhibition of cell growth is not a result of membrane damage induced by prooxidants released from anthracenones. Hydroxyl-radical generation as measure of the prooxidant potential of the compounds was determined by deoxyribose degradation. The most potent analogues of this series were equally potent as anthralin against 12(S)-HETE biosynthesis and keratinocyte proliferation, while oxygen-radical generation and the resulting damage to cell membrane was strongly reduced as compared to the antipsoriatic drug.
使用混合酸酐偶联法或Boc保护的恶唑烷二酮合成了带有10-α-氨基酰基的1,8-二羟基-9(10H)-蒽酮。对这些新型蒽酮进行了评估，考察其对小鼠表皮匀浆中12(S)-羟基二十碳四烯酸（12(S)-HETE）生物合成的抑制作用以及对HaCaT角质形成细胞生长的抑制作用。还测试了这些细胞对该系列中最有效成员作用于质膜完整性的敏感性，以确认细胞生长的抑制不是由蒽酮释放的促氧化剂引起的膜损伤所致。通过脱氧核糖降解测定作为化合物促氧化潜力指标的羟基自由基生成情况。该系列中最有效的类似物在抑制12(S)-HETE生物合成和角质形成细胞增殖方面与地蒽酚同样有效，而与抗银屑病药物相比，氧自由基生成以及由此对细胞膜造成的损伤则大大减少。
