Müller K, Altmann R, Prinz H
Westfälische Wilhelms-Universität Münster, Institut für Pharmazeutische Chemie, Hittorfstrasse 58-62, D-48149, Münster, Germany.
Eur J Med Chem. 2001 Jun;36(6):569-75. doi: 10.1016/s0223-5234(01)01248-x.
A series of 2-arylmethyl-substituted anthracenones were synthesized and tested as inhibitors of three types of 12-lipoxygenase isoforms in epidermal homogenate of mice, bovine platelets and porcine leucocytes. Their inhibitory activities were compared with those to inhibit the 5-lipoxygenase enzyme in bovine leucocytes. Structure-activity relationships are described with particular emphasis on modifications of the terminal aryl nucleus. The ability of the compounds to selectively inhibit the 12-lipoxygenase enzymes was dependent on a high overall lipophilicity of the inhibitor, whereas compounds with decreased lipophilicity were also inhibitors of the 5-LO enzyme. Among the more lipophilic inhibitors, the unsubstituted 2-phenylmethyl analogue 6a as well as the carboxylic acid ester 6q appeared to be selective inhibitors of platelet-type 12-LO isoform.
合成了一系列2-芳基甲基取代的蒽醌，并在小鼠表皮匀浆、牛血小板和猪白细胞中作为三种12-脂氧合酶同工型的抑制剂进行了测试。将它们的抑制活性与在牛白细胞中抑制5-脂氧合酶的活性进行了比较。描述了构效关系，特别强调了末端芳环的修饰。化合物选择性抑制12-脂氧合酶的能力取决于抑制剂的高整体亲脂性，而亲脂性降低的化合物也是5-LO酶的抑制剂。在亲脂性更强的抑制剂中，未取代的2-苯基甲基类似物6a以及羧酸酯6q似乎是血小板型12-LO同工型的选择性抑制剂。
