Eisenbrand Gerhard, Hippe Frankie, Jakobs Sandra, Muehlbeyer Stephan
Division of Food Chemistry and Environmental Toxicology, Department of Chemistry, University of Kaiserslautern, P.O. Box 3049, 67663, Kaiserslautern, Germany.
J Cancer Res Clin Oncol. 2004 Nov;130(11):627-35. doi: 10.1007/s00432-004-0579-2. Epub 2004 Aug 31.
Indirubin, a 3, 2' bisindole isomer of indigo, has originally been identified as the active principle of a traditional Chinese preparation and has been proven to exhibit antileukemic effectiveness in chronic myelocytic leukemia. Indirubin was detected to represent a novel lead structure with potent inhibitory potential towards cyclin-dependent kinases (CDKs) resulting from high affinity binding into the enzymes ATP binding site. This seminal finding triggered our research to improve the pharmacological activities of the parent molecule within comprehensive structure-activity studies. Molecular modifications made novel anticancer compounds accessible with strongly improved CDK inhibitory potential and with broad spectrum antitumour activity. This novel family of compounds holds strong promise for clinical anticancer activity and might be useful also in several important noncancer indications, including Alzheimer's disease or diabetes.
靛玉红是靛蓝的一种3,2'-双吲哚异构体，最初被鉴定为一种传统中药制剂的活性成分，并已被证明在慢性粒细胞白血病中具有抗白血病作用。检测发现靛玉红是一种新型先导结构，因其与细胞周期蛋白依赖性激酶（CDK）的ATP结合位点具有高亲和力结合，从而对CDK具有强大的抑制潜力。这一开创性的发现引发了我们在全面的构效关系研究中改善母体分子药理活性的研究。分子修饰使新型抗癌化合物得以获得，其对CDK的抑制潜力大大提高，且具有广谱抗肿瘤活性。这一新型化合物家族在临床抗癌活性方面极具前景，可能在包括阿尔茨海默病或糖尿病在内的几种重要非癌症适应症中也有用处。
