SYNTHESIS OF NEW NITRONES TARGETING MITOCHONDRIA WITH LOW CYTOTOXICITY
| Autor: | Sophie Thétiot-Laurent, Caroline Delehedde, Mathieu Esgulian, Mathieu Cassien, Marcel Culcasi, Sylvia Pietri |
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| Přispěvatelé: | Institut de Chimie Radicalaire (ICR), Aix Marseille Université (AMU)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), ANR-17-CE34-0006,MITODIAPM,Sondes mitochondriales et dispositifs de génération d'aérosols pour l'étude du stress oxydant et des dysfonctionnements cardiométaboliques induits par l'inhalation de faibles niveaux de particules ultrafines de pesticides chez l'animal(2017), Thétiot-Laurent, Sophie, Sondes mitochondriales et dispositifs de génération d'aérosols pour l'étude du stress oxydant et des dysfonctionnements cardiométaboliques induits par l'inhalation de faibles niveaux de particules ultrafines de pesticides chez l'animal - - MITODIAPM2017 - ANR-17-CE34-0006 - AAPG2017 - VALID |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: | |
| Zdroj: | 9th World Congress on Targeting Mitochondria 9th World Congress on Targeting Mitochondria, Oct 2018, Berlin, Germany HAL |
| Popis: | International audience; Introduction: 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.Materiel-Methods: 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.Results: a) synthesis of a series of vectorized PPNs with different linkers and vectors, b) spin-adducts EPR-parameters determination with various FR, c) comparative cytotoxicity studies in various normal and cancer cells and mitochondria permeation according to vectors.Conclusion: 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. |
| Databáze: | OpenAIRE |
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