Design, Synthesis and Structure-Activity Relationship Studies of Novel 4 (1-adamantyl) Phenyl Analogues as HIF-1α Inhibitors

Med Chem. 2016;12(4):338-46. doi: 10.2174/1573406412666151109113007.

Abstract

Hypoxia inducible factor-1 (HIF-1) is a key mediator during cancer cells to adapt tumor hypoxic condition. In this study, a series of adamantane-based compounds were synthesized and evaluated as potential inhibitors of HIF-1α. Examination of their structure-activity relationship (SAR) identified the adamantane-containing indole derivative 20a as a potent inhibitor of HIF-1α in Hep3B cell lines under tumor hypoxia (IC50 = 0.02 µM). The study herein may provide valuable information for the development of novel therapeutics against cancer and tumor angiogenesis.

MeSH terms

  • Acetanilides / chemical synthesis
  • Acetanilides / pharmacology*
  • Acetanilides / toxicity
  • Adamantane / analogs & derivatives*
  • Adamantane / chemical synthesis
  • Adamantane / pharmacology*
  • Adamantane / toxicity
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / toxicity
  • Cell Line, Tumor
  • Drug Screening Assays, Antitumor
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / antagonists & inhibitors*
  • Structure-Activity Relationship
  • Tumor Hypoxia

Substances

  • Acetanilides
  • Antineoplastic Agents
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • methyl 3-(2-(2-(3-(1H-indol-3-yl)acrylamido)-4-(adamantan-1-yl)phenoxy)acetamido)benzoate
  • Adamantane