The synthesis, cytotoxicity and inhibition of CDK8 by thirteen analogs of cortistatin A are reported. These efforts revealed that the analogs with either a 6- or 7-isoquinoline or 5-indole side chain in the 17-position are the most promising anti-proliferative agents. These compounds showed potent cytotoxic effects in CEM, HeLa and HMEC-1 cells. All three compounds exhibited IC50 values < 10µM. The most interesting 10l analog exhibited an IC50 value of 0.59 µM towards the human dermal microvascular endothelial cell line (HMEC-1), significantly lower than the reference standard 2-methoxyestradiol. At a concentration at 50 nM the most potent 10h compound reduced the activity of CDK8 to 35%.

中文翻译：

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双脱氢表雄酮类似物作为潜在的新型抗癌剂的合成和生物学评价

报告了 13 种皮质抑素 A 类似物对 CDK8 的合成、细胞毒性和抑制作用。这些努力表明，在 17 位具有 6-或 7-异喹啉或 5-吲哚侧链的类似物是最有前途的抗增殖剂。这些化合物在 CEM、HeLa 和 HMEC-1 细胞中显示出有效的细胞毒性作用。所有三种化合物的 IC50 值均小于 10µM。最有趣的 10l 类似物对人真皮微血管内皮细胞系 (HMEC-1) 的 IC50 值为 0.59 µM，明显低于参考标准 2-甲氧基雌二醇。在 50 nM 的浓度下，最有效的 10 小时化合物将 CDK8 的活性降低到 35%。