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

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.

• Authors: Ying-Rui Yang, Jin-Lian Wei, Xiao-Fei Mo, Zhen-Wei Yuan, Jia-Lin Wang, Chao Zhang, Yi-Yue Xie, Qi-Dong You, Hao-Peng Sun
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 26 Issue 11 Pg. 2713-8 (06 01 2016) ISSN: 1464-3405 [Electronic] England
• PMID: 27101893 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016. Published by Elsevier Ltd.

Chemical References

• Antineoplastic Agents
• Benzofurans
• Hypoxia-Inducible Factor 1
• Tumor Suppressor Protein p53
• benzofuran

Topics

• Antineoplastic Agents (chemical synthesis, pharmacology)
• Benzofurans (chemical synthesis, chemistry, pharmacology)
• Cell Cycle Checkpoints (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Dose-Response Relationship, Drug
• Drug Discovery
• Drug Screening Assays, Antitumor
• HCT116 Cells
• Humans
• Hypoxia-Inducible Factor 1 (antagonists & inhibitors)
• MCF-7 Cells
• Molecular Structure
• Neoplasms (drug therapy, metabolism, pathology)
• Structure-Activity Relationship
• Tumor Suppressor Protein p53 (antagonists & inhibitors, deficiency)