2. Academic Validation
  3. Design, synthesis, and evaluation of benzofuran derivatives as novel anti-pancreatic carcinoma agents via interfering the hypoxia environment by targeting HIF-1α pathway

Design, synthesis, and evaluation of benzofuran derivatives as novel anti-pancreatic carcinoma agents via interfering the hypoxia environment by targeting HIF-1α pathway

  • Eur J Med Chem. 2017 Sep 8:137:45-62. doi: 10.1016/j.ejmech.2017.05.042.
Xiao-Li Xu 1,  Ying-Rui Yang 1,  Xiao-Fei Mo 1,  Jin-Lian Wei 1,  Xiao-Jin Zhang 2,  Qi-Dong You 3
Affiliations

Affiliations

  • 1 State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China; Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China.
  • 2 State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China; Department of Organic Chemistry, School of Science, China Pharmaceutical University, Nanjing, 210009, China.
  • 3 State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China; Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China. Electronic address: youqd@163.com.
PMID: 28554092 DOI: 10.1016/j.ejmech.2017.05.042
Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the most common type of pancreatic Cancer, and has still been the medicinal mystery. New drugs and treatment strategies are urgently needed. In this study, 32 benzofuran derivatives are designed, synthesized and evaluated as potential agents against the pancreatic Cancer. Among them, compound 9o with the best physicochemical and pharmacokinetic properties exhibited excellent cytotoxicity against many tumor cell lines. In vivo study showed that compound 9o dramatically suppressed the tumor growth of nude mice. Furthermore, compound 9o could affect the hypoxia environment through HIF-1α/VEGF pathway, resulting in the anti-angiogenic activity. These studies indicated that compound 9o was a promising candidate for the treatment of PDAC, deserving further studies.

Keywords

Anti-angiogenesis; Anti-tumor activity; Apoptosis; Benzofuran derivatives; HIF-1α pathway; Pancreatic cancer; Structure-activity relationships.

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