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.

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

Turrin, Giulia
Primo
Writing – Review & Editing
;
Fantinati, Anna
Supervision
;
Cristofori, Virginia;Illuminati, Davide;Preti, Delia
Investigation
;
Morciano, Giampaolo
Methodology
;
Pinton, Paolo
Formal Analysis
;
Agyapong, Esther Densu
Investigation
;
Trapella, Claudio
Penultimo
Conceptualization
;
2024

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.
2024
Turrin, Giulia; Lo Cascio, Ettore; Giacon, Noah; Fantinati, Anna; Cristofori, Virginia; Illuminati, Davide; Preti, Delia; Morciano, Giampaolo; Pinton, Paolo; Agyapong, Esther Densu; Trapella, Claudio; Arcovito, Alessandro
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/2536398
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