Synthesis and biological evaluation of meta-carborane-containing phenoxyacetanilides as inhibitors of hypoxia-inducible factor (HIF)-1 transcriptional activity

• meta-Carboranylphenoxyacetanilides were synthesized by copper-catalyzed coupling.
• Two compounds exhibited inhibition of hypoxia-induced HIF-1 transcription.
• An isobutyl group is essential for their significant inhibitory potency.

meta-Carboranylphenoxyacetanilides were synthesized by copper catalyzed coupling reaction of meta-carborane and phenyl iodides. The synthesized compounds were evaluated for their ability to inhibit hypoxia-induced HIF-1 transcriptional activity using a cell-based reporter gene assay. Among the compounds synthesized, meta-carborane containing phenoxyanilides 2d and 2h, which have an isobutyl group on meta-carborane, exhibited significant inhibition of hypoxia-induced HIF-1 transcriptional activity toward HeLa cell-based reporter gene assay with the IC50 values of 0.73 and 0.55 μM, respectively.

meta-Carboranylphenoxyacetanilides 2d and 2h were synthesized and found to possess significant inhibition of hypoxia-induced HIF-1 transcriptional activity toward HeLa cell-based reporter gene assay with the IC50 values of 0.73 and 0.55 μM, respectively.Figure optionsDownload as PowerPoint slide