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. 2024 Jan 11;67(1):586-602.
doi: 10.1021/acs.jmedchem.3c01792. Epub 2023 Nov 22.

Spiropiperidine-Based Oligomycin-Analog Ligands To Counteract the Ischemia-Reperfusion Injury in a Renal Cell Model

Giulia Turrin  1 , Ettore Lo Cascio  2 , Noah Giacon  2 , Anna Fantinati  3 , Virginia Cristofori  1 , Davide Illuminati  1 , Delia Preti  1 , Giampaolo Morciano  4   5 , Paolo Pinton  4   5 , Esther Densu Agyapong  4 , Claudio Trapella  1   5 , Alessandro Arcovito  2   6
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Spiropiperidine-Based Oligomycin-Analog Ligands To Counteract the Ischemia-Reperfusion Injury in a Renal Cell Model

Giulia Turrin et al. J Med Chem. .

Abstract

Finding a therapy for ischemia-reperfusion injury, which consists of cell death following restoration of blood flowing into the artery affected by ischemia, is a strong medical need. Nowadays, only the use of broad-spectrum molecular therapies has demonstrated a partial efficacy in protecting the organs following reperfusion, while randomized clinical trials focused on more specific drug targets have failed. In order to overcome this problem, we applied a combination of molecular modeling and chemical synthesis to identify novel spiropiperidine-based structures active in mitochondrial permeability transition pore opening inhibition as a key process to enhance cell survival after blood flow restoration. Our results were confirmed by biological assay on an in vitro cell model on HeLa and human renal proximal tubular epithelial cells and pave the way to further investigation on an in vivo model system.

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Conflict of interest statement

The authors declare no competing financial interest.

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