Sissi Claudia, Palumbo Manlio
Department of Pharmaceutical Sciences, University of Padova, Via Marzolo, 5, 35131 Padova, Italy.
Curr Top Med Chem. 2004;4(2):219-30. doi: 10.2174/1568026043451483.
Aza-bioisosteres of anthracene-9,10-diones and of anthrapyrazoles comprise an innovative class of anticancer compounds. They are formally derived by introduction of one or more nitrogens into the carbocyclic ring system of the parent drugs. Bioisosteres exhibit extensive changes in the physico-chemical properties and in the interactions with the pharmacological targets, DNA and DNA-topoisomerase II, when compared to the carbocyclic analogues. A favourable spectrum of activity, reduced side effects and a unique tropism for solid tumors make the new derivatives a very interesting family of drugs. In particular, a 2-aza-anthracene-9,10-dione and a 9-aza-anthrapyrazole derivative are presently undergoing advanced clinical trials and appear to be promising in view of their approval as anticancer drugs.
蒽-9,10-二酮和蒽并吡唑的氮杂生物电子等排体构成了一类创新的抗癌化合物。它们是通过在母体药物的碳环系统中引入一个或多个氮原子而正式衍生出来的。与碳环类似物相比，生物电子等排体在物理化学性质以及与药理靶点DNA和DNA拓扑异构酶II的相互作用方面表现出广泛的变化。良好的活性谱、减少的副作用以及对实体瘤独特的趋向性使得这些新衍生物成为一类非常有吸引力的药物。特别是，一种2-氮杂蒽-9,10-二酮和一种9-氮杂蒽并吡唑衍生物目前正在进行晚期临床试验，鉴于它们有望获批成为抗癌药物，前景十分广阔。
