Hypoxia-inducible factor 1α (HIF-1α) is a known regulator of tumor cell proliferation, migration, and angiogenesis. The presence of a high concentration of HIF-1α is positively correlated with the severity of cancer. Therefore, the inhibition of this pathway represents an important therapeutic target for the treatment of various types of cancer. Here, we designed and synthesized 30 panaxadiol (PD) derivatives and evaluated their inhibitory activities against HIF-1α transcription. Of these, compound 3l exhibited the most promising inhibitory activity (IC₅₀ = 3.7 µM) and showed significantly decreased cytotoxicity compared with PD. Compound 9e exhibited the strongest cytotoxic effect and may be considered for further preclinical development.

缺氧诱导因子1α（HIF-1α）是已知的肿瘤细胞增殖，迁移和血管生成的调节剂。高浓度的HIF-1α的存在与癌症的严重程度呈正相关。因此，对该途径的抑制代表了用于治疗各种类型癌症的重要治疗靶标。在这里，我们设计和合成了30种人参二醇（PD）衍生物，并评估了其对HIF-1α转录的抑制活性。在这些化合物中， 与PD相比，化合物3l表现出最有希望的抑制活性（IC ₅₀ = 3.7 µM），并且显示出明显降低的细胞毒性。化合物9e 表现出最强的细胞毒性作用，可以考虑用于进一步的临床前开发。