Chalcone-based inhibitors against hypoxia-inducible factor 1-Structure activity relationship studies

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:21

Article

Srinivasan, Balasubramanian¹  Johnson, Thomas E.¹  Xing, Chengguo¹ 

[1] Univ Minnesota, Coll Pharm, Dept Med Chem, Minneapolis, MN 55455 USA

关键词: HIF-1;    Inhibitor;    Cancer;    Chalcone;   

DOI  :  10.1016/j.bmcl.2010.10.063

来源: Elsevier

【 摘 要 】

Many tumor tissues are under hypoxic conditions. Activating hypoxia-inducible factor 1 (HIF-1), a transcription factor, is a major mechanism for tumor cells to survive and even to evade other tissues. Therefore inhibiting HIF-1 is a potential strategy to help improve cancer treatment. Chalcone is a promising template to develop HIF-1 inhibitor because quite a few of chalcone-based compounds reveal moderate HIF-1 inhibitory activity and many chalcone-based compounds demonstrate promising anticancer activities in various animal models. However, there are no reports about the structure-activity relationship of chalcone compounds with respect to HIF-1 inhibition. This study reports the HIF-1 inhibitory activities of a panel of chalcones, identifies a few lead candidates of single-digit micromolar potency, and determines important structural modifications. Published by Elsevier Ltd.

【 授权许可】

Free