Interdisciplinary Program of Biological Function Molecules, College of Integration Science, Yanbian University, Yanji 133002, China.
Key Laboratory of Natural Medicines of the Changbai Mountain Ministry of Education, College of Pharmacy, Yanbian University, Yanji 133002, China.
Fitoterapia. 2024 Sep;177:106052. doi: 10.1016/j.fitote.2024.106052. Epub 2024 Jun 6.
Hypoxia-inducing factor-1α (HIF-1α) is overexpressed in variety of tumor patients and plays an important role in the regulation of hypoxia response in tumor cells. Therefore, its inhibitors have become one of the targets for the treatment of a variety of cancers. Two series of panaxadiol (PD) ester derivatives containing pyrazole (18a-j) and pyrrole (19a-n) moiety were synthesized and their HIF-1α inhibitory activities were evaluated. Among all the target compouds, compounds 18c, 19d, and 19n (IC = 8.70-10.44 μM) showed better HIF-1α inhibitory activity than PD (IC = 13.35 μM). None of these compounds showed cytotoxicity above 100 μM and inhibited HIF-1α transcription in a dose-dependent manner. These compounds showed good antitumor activity and provide lead compounds for further design and activity study of PD ester derivatives.
缺氧诱导因子-1α（HIF-1α）在多种肿瘤患者中过度表达，在肿瘤细胞的低氧反应调节中发挥重要作用。因此，其抑制剂已成为治疗多种癌症的靶点之一。合成了含有吡唑（18a-j）和吡咯（19a-n）部分的两种panaxadiol（PD）酯衍生物系列，并对其 HIF-1α 抑制活性进行了评价。在所有目标化合物中，化合物 18c、19d 和 19n（IC=8.70-10.44μM）对 HIF-1α 的抑制活性优于 PD（IC=13.35μM）。这些化合物在 100μM 以上均无细胞毒性，并呈剂量依赖性抑制 HIF-1α 转录。这些化合物表现出良好的抗肿瘤活性，为 PD 酯衍生物的进一步设计和活性研究提供了先导化合物。
