2. Academic Validation
  3. Synthesis and evaluation of HIF-1α inhibitory activities of novel panaxadiol derivatives

Synthesis and evaluation of HIF-1α inhibitory activities of novel panaxadiol derivatives

  • Bioorg Med Chem Lett. 2020 Dec 15;30(24):127652. doi: 10.1016/j.bmcl.2020.127652.
Da-Yuan Wang 1,  Yan-Wei Li 1,  Lin-Hao Zhang 1,  Li-Yan Lv 1,  Yu-Qing Zhao 2,  Xue-Jun Jin 3,  Hu-Ri Piao 4
Affiliations

Affiliations

  • 1 Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Yanbian University, Yanji 133002 China.
  • 2 Shenyang Pharmaceutical University, Shenyang 110016, China; Key Laboratory of Structure-based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address: zyq4885@126.com.
  • 3 Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Yanbian University, Yanji 133002 China. Electronic address: xjjin@ybu.edu.cn.
  • 4 Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Yanbian University, Yanji 133002 China. Electronic address: piaohr@ybu.edu.cn.
PMID: 33130293 DOI: 10.1016/j.bmcl.2020.127652
Abstract

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.

Keywords

Anti-tumor; Cytotoxicity; HIF-1α inhibitor; Panaxadiol.

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