Design, Synthesis and Biological Evaluation of Novel HIF1α Inhibitors

作者：Masoud, Georgina N.; Wang, Jin; Chen, Jianjun; Miller, Duane; Li, Wei^*

来源：Anticancer Research, 2015, 35(7): 3849-3859.

• Hypoxia
• benzimidazoles
• HIF-1 alpha inhibitors
• breast cancer

Elevated levels of hypoxia inducible factor-1 (HIF1) are linked to tumor metastasis, angiogenesis, poor patient prognosis and response to chemotherapy. HIF1 alpha is a master regulator of the hypoxic response, including in cancer cells, through transcriptional activation of several target genes. Previously, we identified compound CJ-3k with high anti-HIF1 alpha activity based on the structure of a well-known HIF1 alpha inhibitor, YC-1. In this study, the CJ-3k scaffold was systematically modified to explore the structure-activity relationships. Fifty-three new CJ-3k analogs were synthesized and screened for their anti-HIF-1 alpha activity in a luciferase-transfected human breast cancer cell line (MDA-MB-231). Some of these new analogs have a significantly greater activity than that of CJ-3k and hold potential for development as new therapeutic agents for the treatment of cancer.

• 出版日期2015-7