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

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.