TY - JOUR
T1 - Spiropiperidine-Based Oligomycin-Analog Ligands To Counteract the Ischemia-Reperfusion Injury in a Renal Cell Model
AU - Turrin, G.
AU - Lo, Cascio E.
AU - Giacon, N.
AU - Fantinati, A.
AU - Cristofori, V.
AU - Illuminati, D.
AU - Preti, D.
AU - Morciano, G.
AU - Pinton, P.
AU - Agyapong, E. D.
AU - Trapella, C.
AU - Arcovito, Alessandro
PY - 2024
Y1 - 2024
N2 - 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.
AB - 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.
KW - Ischemia Reperfusion Injury
KW - Molecular Dynamics
KW - Ischemia Reperfusion Injury
KW - Molecular Dynamics
UR - https://publicatt.unicatt.it/handle/10807/263374
UR - https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=85179613624&origin=inward
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85179613624&origin=inward
U2 - 10.1021/acs.jmedchem.3c01792
DO - 10.1021/acs.jmedchem.3c01792
M3 - Article
SN - 0022-2623
VL - 67
SP - 586
EP - 602
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
IS - 1
ER -