Discovery of bicyclo[3,3,1]non-2-ene as a novel skeleton for HIF-1 inhibitors

Bioorganic & Medicinal Chemistry
Hiroki UedaHiroyuki Nakamura

Abstract

Bicyclo[3,3,1]non-2-ene was used as a novel three-dimensional skeleton for the design and synthesis of hypoxia-inducible factor (HIF)-1 inhibitors. Among the compounds synthesized, compound 4b was found to be a potent inhibitor of HIF-1α protein accumulation under hypoxia and inhibited HIF-1α transcriptional activity in HeLa (human cervical carcinoma) cells (half maximal inhibitory concentration [IC50] = 3.0 μM). The inhibition of HIF-1α accumulation induced by compound 4b was attenuated by treating the cells with MG132, a proteasome inhibitor, in a concentration-dependent manner, indicating that the compound 4b induces oxygen-independent proteasomal degradation of HIF-1α.

Associated Datasets

Citations

Jun 2, 2021·Chemistry : a European Journal·Kohei UmederaHiroyuki Nakamura
Dec 18, 2021·Scientific Reports·Yasunobu AsawaHiroyuki Nakamura

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