1. Design, synthesis, and evaluation of benzofuran derivatives as novel anti-pancreatic carcinoma agents via interfering the hypoxia environment by targeting HIF-1α pathway.
- Author
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Xu XL, Yang YR, Mo XF, Wei JL, Zhang XJ, and You QD
- Subjects
- Animals, Antineoplastic Agents chemical synthesis, Antineoplastic Agents chemistry, Benzofurans chemical synthesis, Benzofurans chemistry, Cell Proliferation drug effects, Dose-Response Relationship, Drug, Drug Screening Assays, Antitumor, Humans, Hypoxia-Inducible Factor 1, alpha Subunit metabolism, Mice, Molecular Structure, Neoplasms, Experimental drug therapy, Neoplasms, Experimental metabolism, Neoplasms, Experimental pathology, Pancreatic Neoplasms metabolism, Pancreatic Neoplasms pathology, Structure-Activity Relationship, Tumor Cells, Cultured, Pancreatic Neoplasms, Antineoplastic Agents pharmacology, Benzofurans pharmacology, Drug Design, Hypoxia metabolism, Hypoxia-Inducible Factor 1, alpha Subunit antagonists & inhibitors, Pancreatic Neoplasms drug therapy
- 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., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)
- Published
- 2017
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