2. Academic Validation
  3. Total synthesis and biological evaluation of 7-hydroxyneolamellarin A as hypoxia-inducible factor-1α inhibitor for cancer therapy

Total synthesis and biological evaluation of 7-hydroxyneolamellarin A as hypoxia-inducible factor-1α inhibitor for cancer therapy

  • Bioorg Med Chem Lett. 2021 Oct 15;50:128338. doi: 10.1016/j.bmcl.2021.128338.
Guangzhe Li 1,  Yujie Shao 2,  Yue Pan 2,  Yueqing Li 2,  Yang Wang 3,  Liu Wang 2,  Xu Wang 2,  Kun Shao 3,  Shisheng Wang 2,  Naixuan Liu 2,  Jingdong Zhang 4,  Weijie Zhao 2,  Hiroyuki Nakamura 5
Affiliations

Affiliations

  • 1 State Key Laboratory of Fine Chemicals, Department of Pharmaceutical Sciences, School of Chemical Engineering, Dalian University of Technology, Dalian 116024, China. Electronic address: [email protected].
  • 2 State Key Laboratory of Fine Chemicals, Department of Pharmaceutical Sciences, School of Chemical Engineering, Dalian University of Technology, Dalian 116024, China.
  • 3 State Key Laboratory of Fine Chemicals, School of Chemical Engineering, Dalian University of Technology, Dalian 116024, China.
  • 4 Medical Oncology Department of Gastrointestinal Cancer, Liaoning Cancer Hospital & Institute, Cancer Hospital of China Medical University, Shenyang 110042, China.
  • 5 Laboratory for Chemistry and Life Science, Institute of Innovative Research, Tokyo Institute of Technology, Nagatsuta-cho, Midori-ku, Yokohama 226-8503, Japan.
PMID: 34469710 DOI: 10.1016/j.bmcl.2021.128338
Abstract

7-Hydroxyneolamellarin A (7-OH-Neo A, 1), a natural marine product derived from Sponge Dendrilla nigra, was first synthesized with 10% overall yield under the instruction of convergent synthetic strategy. We found that 7-OH-Neo A could attenuate the accumulation of hypoxia-inducible factor-1α (HIF-1α) protein and inhibit vascular epidermal growth factor (VEGF) transcriptional activity, showing well inhibitory effect on HIF-1 signaling pathway. Meantime, 7-OH-Neo A had the well anti-tumor activities, such as inhibiting tumor angiogenesis, proliferation, migration and invasion. More importantly, 7-OH-Neo A exhibited profound anti-tumor effect in mice breast Cancer model by suppressing the accumulation of HIF-1α in tumor tissue. Mechanism study demonstrated that 7-OH-Neo A might target the protein with the ability of stabilizing HIF-1α in hypoxia. Due to the excellent water solubility, superior anti-tumor activity and good biocompatibility, 7-OH-Neo A shows the promising potential for being exploited as an anti-tumor agent in near future.

Keywords

7-Hydroxyneolamellarin A; Anti-tumor; HIF-1α inhibition; Total synthesis.

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