%0 Unpublished work %T Targeting mitochondria with novel, differently vectorized linear phosphorylated nitrones: %+ Institut de Chimie Radicalaire (ICR) %A Delehedde, Caroline %A Thétiot-Laurent, Sophie %A Esgulian, Mathieu %A Chocry, Mathieu %A Rockenbauer, Antal %A Pietri, Sylvia %A Culcasi, Marcel %8 2020 %D 2020 %K Mitochondria-targeted nitrones %K 31P NMR %K EPR spin trapping %K mitochondrial permeability %K H2O2-induced apoptosis %Z Chemical Sciences/Organic chemistryPreprints, Working Papers, ... %X The free radicals (FR) occurrence in biological signalling or as pathologies triggers is well-documented and the design of specific scavengers to limit oxidative stress is enthralling. Because FR become inactivated upon addition to nitrones, efforts have focused on developing alpha-phenyl-N-tert-butylnitrone derivatives (PBNs) with promising pre-clinical data. To improve efficacy, a new generation of nitrones derived from 2-(diethoxyphosphoryl)-N-(benzylidene)propan-2-amine-N-oxide (PPNs) incorporating an antioxidant framework, gave rise to multipotent drugs exhibiting EPR-spin-trapping properties. As mitochondrial dysfunction is involved in many disorders, efforts have been concentrated on developing tools (pH probes) or pharmacological agents targeting-mitochondria. A series of mitochondria-targeted PPNs was synthesized based on the improved biocompatibility of P-containing nitrones and the expected benefits of introducing a cationic vector. Spin-adducts EPR-parameters toward biologically-relevant FR were established. Cytotoxicity was determined on cells and mitochondria-permeation assessed in isolated rat organs. New mitochondria-targeting nitrones appeared as lower cytotoxic alternative to the commonly used mito-PBN and were safely applied for investigating the anticancer-mechanism of new drugs impacting mitochondria. %G English %2 https://amu.hal.science/hal-03081866v2/document %2 https://amu.hal.science/hal-03081866v2/file/Preprint_nitrones2.pdf %L hal-03081866 %U https://amu.hal.science/hal-03081866