A series of 18β-glycyrrhetinic acid (GA) conjugated aminobenzothiazole derivatives were designed, synthesized and evaluated for disruption activity of Hsp90-Cdc37 as well as the effects of in vitro cell migration. These compounds exhibited relatively good disruption activity against Hsp90-Cdc37 with IC₅₀ values in low micromolar range. A docking study of the most active compound 11g revealed key interactions between 11g and Hsp90-Cdc37 complex in which the benzothiazole moiety and the amine chain group were important for improving activity. It is noteworthy that further antitumor activity screening revealed that some compounds exhibited better inhibitory activity than the commercial anticancer drug 5-FU and showed potent suppression activity against drug-resistant cancer cells. In particular, compound 11 g appeared to be the most potent compound against the A549 cell line, at least partly, by inhibition of the activity of Hsp90 and apoptosis induction. The treatment of A549 cells with compound 11g resulted in inhibition of in vitro cell migration through wound healing assay and S phase of cell cycle arrested. In addition, 11g-induced apoptosis was significantly facilitated in A549 cells. Thus, we conclude that GA aminobenzothiazole derivatives may be the potential Hsp90-Cdc37 disruptors with the ability to suppress cells migration and reversed drug-resistant.

设计，合成并评估了一系列18β-甘草次酸（GA）共轭的氨基苯并噻唑衍生物，并评估了其对Hsp90-Cdc37的破坏活性以及体外细胞迁移的影响。这些化合物对Hsp90-Cdc37表现出相对较好的破坏活性，IC ₅₀值在低微摩尔范围内。最活跃的化合物的对接研究11克透露之间的关键交互11克Hsp90-Cdc37配合物，其中苯并噻唑部分和胺链基对提高活性很重要。值得注意的是，进一步的抗肿瘤活性筛选显示，某些化合物显示出比市售抗癌药物5-FU更好的抑制活性，并显示出对耐药癌细胞的有效抑制活性。特别地，至少部分地通过抑制Hsp90的活性和诱导凋亡，化合物11g似乎是针对A549细胞系的最有效的化合物。用化合物11g处理A549细胞通过伤口愈合试验抑制了体外细胞迁移，并阻止了S期细胞周期。另外11g诱导的凋亡在A549细胞中得到显着促进。因此，我们得出结论，GA氨基苯并噻唑衍生物可能是潜在的Hsp90-Cdc37破坏者，具有抑制细胞迁移和逆转耐药性的能力。