Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Yanbian University, Yanji 133002 China.
Shenyang Pharmaceutical University, Shenyang 110016, China; Key Laboratory of Structure-based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China.
Bioorg Med Chem Lett. 2020 Dec 15;30(24):127652. doi: 10.1016/j.bmcl.2020.127652. Epub 2020 Oct 29.
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 (IC = 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）是一种已知的肿瘤细胞增殖、迁移和血管生成的调节剂。HIF-1α 浓度高与癌症的严重程度呈正相关。因此，抑制这条通路是治疗各种类型癌症的一个重要治疗靶点。在这里，我们设计并合成了 30 种人参二醇（PD）衍生物，并评估了它们对 HIF-1α 转录的抑制活性。其中，化合物 3l 表现出最有希望的抑制活性（IC=3.7µM），与 PD 相比，其细胞毒性显著降低。化合物 9e 表现出最强的细胞毒性作用，可能考虑进一步进行临床前开发。
