Antipsoriatic Anthrones with Modulated Redox Properties. 5. Potent Inhibition of Human Keratinocyte Growth, Induction of Keratinocyte Differentiation, and Reduced Membrane Damage by Novel 10-Arylacetyl-1,8-dihydroxy-9(10<i>H</i>)-anthracenones
作者:Klaus Müller、Hans Reindl、Klaus Breu
DOI:10.1021/jm001073w
日期:2001.3.1
human keratinocyte growth as the antipsoriatic agent anthralin. Furthermore, improved ratio of antiproliferative activity to cytotoxicity is demonstrated by the reduced potential of the novel analogues to induce membrane damage, which is a benefit of their reduced ability to generate oxygen radicals as documented by deoxyribose degradation. Second, analogue 3o bearing a hydroxamate functional group was
描述了一系列新型的10-芳基乙酰基-1,8-二羟基-9(10H)-蒽酮的合成和构效关系(SAR)。在吡啶存在下或通过偶联剂二环己基碳二亚胺(DCC)分别用合适的芳基乙酰氯或芳酸对蒽环素进行酰化,提供了这种结构的抗银屑病药物。在针对银屑病三个重要方面的补充检测中评估了潜在的银屑病活性。首先,鉴定了几种化合物,它们与抗银屑病药蒽林一样具有与人角质形成细胞生长抑制剂相同的作用。此外,新的类似物诱导膜损伤的潜力降低,证明了抗增殖活性与细胞毒性的比率提高了,如脱氧核糖降解所证明的,这是它们降低产生氧自由基的能力的益处。第二,带有异羟肟酸酯官能团的类似物3o除其出色的抗增殖活性外,还是LTB(4)生物合成的高效抑制剂。这些抑制剂的角质形成细胞生长和LTB(4)生物合成相对于10-苯基乙酰基侧链中对位取代的性质的SARs进行了讨论。第三,还评估了化合物诱导角质形成细胞中玉米化包膜蛋白形成的能力。对于许多