Institut für Pharmazeutische und Medizinische Chemie, PharmaCampus, Westfälische Wilhelms-Universität Münster, Corrensstr. 48, 48149 Münster, Germany.
Faculty of Pharmacy, 17 April street, Damascus University, Damascus P.O. Box 9411, Syria.
Molecules. 2019 Dec 26;25(1):97. doi: 10.3390/molecules25010097.
Casein kinase II (CK2) is an intensively studied enzyme, involved in different diseases, cancer in particular. Different scaffolds were used to develop inhibitors of this enzyme. Here, we report on the synthesis and biological evaluation of twenty phenolic, ketonic, and -quinonic indeno[1,2-]indole derivatives as CK2 inhibitors. The most active compounds were 5-isopropyl-1-methyl-5,6,7,8-tetrahydroindeno[1,2-]indole-9,10-dione and 1,3-dibromo-5-isopropyl-5,6,7,8-tetrahydroindeno[1,2-]indole-9,10-dione with identical IC values of 0.11 µM. Furthermore, the development of a QSAR model based on the structure of indeno[1,2-]indoles was performed. This model was used to predict the activity of 25 compounds with naphtho[2,3-]furan-4,9-dione derivatives, which were previously predicted as CK2 inhibitors via a molecular modeling approach. The activities of four naphtho[2,3-]furan-4,9-dione derivatives were determined in vitro and one of them (-isopentyl-2-methyl-4,9-dioxo-4,9-dihydronaphtho[2,3-]furan-3-carboxamide) turned out to inhibit CK2 with an IC value of 2.33 µM. All four candidates were able to reduce the cell viability by more than 60% after 24 h of incubation using 10 µM.
酪蛋白激酶 2（CK2）是一种研究较为深入的酶，参与多种疾病，尤其是癌症。不同的支架被用于开发这种酶的抑制剂。在这里，我们报告了二十种酚类、酮类和 -醌类茚并[1,2-]吲哚衍生物作为 CK2 抑制剂的合成和生物学评价。最活跃的化合物是 5-异丙基-1-甲基-5,6,7,8-四氢茚并[1,2-]吲哚-9,10-二酮 和 1,3-二溴-5-异丙基-5,6,7,8-四氢茚并[1,2-]吲哚-9,10-二酮，其 IC 值相同，均为 0.11 µM。此外，还基于茚并[1,2-]吲哚的结构开发了一个 QSAR 模型。该模型用于预测 25 种具有萘并[2,3-]呋喃-4,9-二酮衍生物的化合物的活性，这些化合物先前通过分子建模方法预测为 CK2 抑制剂。体外测定了四种萘并[2,3-]呋喃-4,9-二酮衍生物的活性，其中一种（-异戊基-2-甲基-4,9-二氧代-4,9-二氢萘并[2,3-]呋喃-3-甲酰胺）对 CK2 的抑制作用的 IC 值为 2.33 µM。在使用 10 µM 孵育 24 小时后，所有四个候选化合物都能够使细胞活力降低 60%以上。
