Department of Pediatric Hematology/Oncology, Helios Clinic Schwerin, Wismarsche Straße 393-397, 19055 Schwerin, Germany.
Department of Pediatric Hematology/Oncology, Municipal Clinics of Cologne, Children's Hospital of the City Cologne, Amsterdamer Straße 59, 50735 Cologne, Germany.
Molecules. 2022 Aug 8;27(15):5038. doi: 10.3390/molecules27155038.
and its indigo dyes have already provided highly active anti-leukaemic lead compounds, with the focus mainly being on indirubin, whereas indigo itself is inactive. There are many more indigoids to find in this plant extract, for example, quingdainone, an indigoid derived from tryptanthrin. We present here a new synthesis of hitherto neglected substituted quingdainones, which is very necessary due to their poor solubility behaviour, and a structure-dependent anti-leukaemic activity study of a number of compounds. Substituted α-phenylaminoacrylic acid was synthesised by hydrogen sulfide extrusion from an analogue mercaptoacetic acid, available from the condensation of rhodanin and a substituted tryptanthrin. It is shown that just improving water solubility does not increase anti-leukaemic activity, since a quingdainone carboxylic acid is inactive compared to dihydroxyquingdainone. The most effective compound, dihydroxyquingdainone with an AC of 7.5 µmole, is further characterised, revealing its ability to overcome multidrug resistance in leukaemia cells (Nalm-6/BeKa) with p-glycoprotein expression.
并且其靛蓝染料已经提供了高度活跃的抗白血病先导化合物，主要集中在靛玉红上，而靛蓝本身则没有活性。在这种植物提取物中还有许多其他的靛蓝，例如，qingdainone，一种源自色胺酮的靛蓝。我们在这里提出了一种新的合成方法，用于合成迄今为止被忽视的取代的 qingdainones，这是非常必要的，因为它们的溶解度很差，并且对一些化合物的结构依赖性抗白血病活性进行了研究。取代的α-苯氨基丙烯酸是通过从类似物巯基乙酸中释放硫化氢合成的，该巯基乙酸可通过罗地那林和取代的色胺酮的缩合得到。结果表明，仅仅提高水溶性并不能提高抗白血病活性，因为与二羟基 quingdainone 相比，qingdainone 羧酸是没有活性的。最有效的化合物，二羟基 quingdainone 的 AC 值为 7.5 µmole，进一步进行了表征，揭示了其在白血病细胞（具有 p-糖蛋白表达的 Nalm-6/BeKa）中克服多药耐药的能力。
