2. Academic Validation
  3. Discovery and optimization of new benzofuran derivatives against p53-independent malignant cancer cells through inhibition of HIF-1 pathway

Discovery and optimization of new benzofuran derivatives against p53-independent malignant cancer cells through inhibition of HIF-1 pathway

  • Bioorg Med Chem Lett. 2016 Jun 1;26(11):2713-8. doi: 10.1016/j.bmcl.2016.03.112.
Ying-Rui Yang 1,  Jin-Lian Wei 1,  Xiao-Fei Mo 1,  Zhen-Wei Yuan 1,  Jia-Lin Wang 1,  Chao Zhang 1,  Yi-Yue Xie 1,  Qi-Dong You 2,  Hao-Peng Sun 3
Affiliations

Affiliations

  • 1 Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China; State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
  • 2 Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China; State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China. Electronic address: youqd@163.com.
  • 3 Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China; State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China; Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China. Electronic address: sunhaopeng@163.com.
PMID: 27101893 DOI: 10.1016/j.bmcl.2016.03.112
Abstract

p53-independent malignant Cancer is still severe health problem of human beings. HIF-1 pathway is believed to play an important role in the survival and developing progress of such cancers. In the present study, with the aim to inhibit the proliferation of p53-independent malignant cells, we disclose the optimization of 6a, the starting compound which is discovered in the screening of in-house compound collection. The structure-activity relationship (SAR) is summarized. The most potent derivative 8d, inhibits the proliferation of both p53-null and p53-mutated cells through inhibition of HIF-1 pathway. Our findings here provide a new chemotype in designing potent Anticancer agent especially against those p53-independent malignant tumors.

Keywords

Antitumor; Apoptosis; Benzofuran; Cycle arrest; HIF-1 inhibition.

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