Heat shock protein 90 (HSP90) inhibition has aroused increasing enthusiasm in antitumor strategies in recent years. According to our previous studies, we synthesized a series of coumarin pyrazoline compounds HCP1-HCP6 that might be HSP90 inhibitors. Interactions between HCP1-HCP6 and HSP90 were examined and antitumor activities of them were investigated in A549 lung cancer cells. Results showed that all the six derivatives could interact with HSP90, in which HCP1 exhibited the best binding ability and inhibited the activity of HSP90. Meanwhile, HCP1-HCP6 reduced the cell viability of A549 cells and HCP1 possessed the lowest IC₅₀ value. Above all HCP1 exerted better HSP90 inhibitory and anticancer effects than our initially identified HSP90 inhibitor DPB. As to the underlying mechanism, HCP1-HCP6 not only induced apoptosis as DPB but also blocked autophagic flux in A549 cells. Therefore, we discovered a novel HSP90 inhibitor HCP1 that had better biological activity and provided us a useful tool to explore the underlying mechanism of lung cancer therapy.

近年来，对热休克蛋白90（HSP90）的抑制引起了人们对抗肿瘤策略的日益高涨的热情。根据我们以前的研究，我们合成了一系列可能是HSP90抑制剂的香豆素吡唑啉化合物HCP1-HCP6。研究了HCP1-HCP6和HSP90之间的相互作用，并研究了它们在A549肺癌细胞中的抗肿瘤活性。结果表明，这六种衍生物均可与HSP90相互作用，其中HCP1表现出最好的结合能力并抑制HSP90的活性。同时，HCP1-HCP6降低了A549细胞的细胞活力，而HCP1的IC ₅₀值最低。首先是HCP1与我们最初确定的HSP90抑制剂DPB相比，HSP90具有更好的HSP90抑制和抗癌作用。至于潜在的机制，HCP1-HCP6不仅诱导DPB凋亡，而且还阻断了A549细胞的自噬通量。因此，我们发现了一种新型的HSP90抑制剂HCP1，它具有更好的生物学活性，并为我们探索肺癌治疗的潜在机制提供了有用的工具。