美诺立尔，一种蒽环类衍生物，通过稳定可裂解复合物来抑制DNA拓扑异构酶II。
Menogaril, an anthracycline derivative, inhibits DNA topoisomerase II by stabilizing cleavable complexes.
作者信息
Ono K, Ikegami Y, Nishizawa M, Andoh T
机构信息
Meiji College of Pharmacy, Department of Hygienic Chemistry, Tokyo.
出版信息
Jpn J Cancer Res. 1992 Sep;83(9):1018-23. doi: 10.1111/j.1349-7006.1992.tb02016.x.
Menogaril, an anthracycline derivative, has been shown to possess antitumor activity in experimental animal systems, and is now under phase II clinical studies. However, its mechanism of action has not been elucidated. We have found that it inhibits the decatenation activity of purified DNA topoisomerase II using kinetoplast DNA from Crithidia fasciculata, its IC50 being 10 microM, which is comparable to that of etoposide. It does not, however, inhibit topoisomerase I activity at concentrations of up to 400 microM. Binding of topoisomerase II with DNA is not affected, but cleavable complex formation is stimulated by the drug. Cleavage site specificity differs from that of 4'-(9-acridinylamino)methanesulfon-m-anisidide. Menogaril was shown to possess a weak double-helix unwinding activity. These findings allow us to classify menogaril as a cleavable complex-stabilizing topoisomerase II inhibitor.
美诺加里尔是一种蒽环类衍生物，已在实验动物系统中显示出抗肿瘤活性，目前正处于II期临床研究阶段。然而，其作用机制尚未阐明。我们发现，它使用来自克氏锥虫的动质体DNA抑制纯化的DNA拓扑异构酶II的解连环活性，其IC50为10微摩尔，与依托泊苷相当。然而，在高达400微摩尔的浓度下，它并不抑制拓扑异构酶I的活性。拓扑异构酶II与DNA的结合不受影响，但药物会刺激可裂解复合物的形成。裂解位点特异性与4'-（9-吖啶基氨基）甲磺酰间茴香胺不同。美诺加里尔显示出较弱的双螺旋解旋活性。这些发现使我们能够将美诺加里尔归类为一种可裂解复合物稳定型拓扑异构酶II抑制剂。
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