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
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Acetanilides / chemical synthesis
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Acetanilides / pharmacology*
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Acetanilides / toxicity
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Adamantane / analogs & derivatives*
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Adamantane / chemical synthesis
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Adamantane / pharmacology*
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Adamantane / toxicity
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Antineoplastic Agents / chemical synthesis
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Antineoplastic Agents / pharmacology*
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Antineoplastic Agents / toxicity
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Cell Line, Tumor
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Drug Screening Assays, Antitumor
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Humans
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Hypoxia-Inducible Factor 1, alpha Subunit / antagonists & inhibitors*
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Structure-Activity Relationship
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Tumor Hypoxia
Substances
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Acetanilides
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Antineoplastic Agents
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HIF1A protein, human
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Hypoxia-Inducible Factor 1, alpha Subunit
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methyl 3-(2-(2-(3-(1H-indol-3-yl)acrylamido)-4-(adamantan-1-yl)phenoxy)acetamido)benzoate
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Adamantane