Chalcone-based inhibitors against hypoxia-inducible factor 1--structure activity relationship studies.
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.
Department of Medicinal Chemistry, College of Pharmacy, University of Minnesota, 308 Harvard St. SE, Minneapolis MN 55455, United States.
Balasubramanian
B
Srinivasan
Thomas E
TE
Johnson
Chengguo
C
Xing
D000818:Animals; D002599:Chalcone / Q000737:chemistry* / Q000494:pharmacology; D051793:Hypoxia-Inducible Factor 1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D011993:Recombinant Fusion Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D013329:Structure-Activity Relationship
D051793:Hypoxia-Inducible Factor 1; D011993:Recombinant Fusion Proteins; D002599:Chalcone