Cytoprotective activities of kinetin purine isosteres
| العنوان: | Cytoprotective activities of kinetin purine isosteres |
|---|---|
| المؤلفون: | Dominik Vítek, Marek Zatloukal, Jiří Voller, Marian Hajduch, Miroslav Strnad, Beata Monfort, Libor Havlíček, Veronika Ručilová, Alena Kadlecová, Prashant Khirsariya, Gabriel Gonzalez, Kamil Paruch, Miroslav Soural, Barbara Maková, Václav Mik, Martina Medvedíková, Barbora Lišková, Benoît D'Autréaux, Zoila Gándara Barreiro |
| المساهمون: | Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Stress Oxydatif et Cancer (SOC), Département Biologie Cellulaire (BioCell), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), ANR-17-CE11-0021,FRATAXUR,Bases moléculaires et structurales de la biogenèse des centres fer-soufre permettant d'élucider la fonction moléculaire de la frataxine(2017) |
| المصدر: | Bioorganic and Medicinal Chemistry Bioorganic and Medicinal Chemistry, Elsevier, 2021, 33, pp.115993. ⟨10.1016/j.bmc.2021.115993⟩ Bioorganic and Medicinal Chemistry, 2021, 33, pp.115993. ⟨10.1016/j.bmc.2021.115993⟩ |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Purine, Cell Survival, [SDV]Life Sciences [q-bio], Clinical Biochemistry, Cytokinin, Pharmaceutical Science, medicine.disease_cause, 01 natural sciences, Biochemistry, Neuroprotection, chemistry.chemical_compound, Structure-Activity Relationship, Drug Discovery, medicine, Humans, bioisostery – Friedreich́s ataxia, Molecular Biology, Cells, Cultured, Mitoprotection – familial dysautonomia, Dose-Response Relationship, Drug, Molecular Structure, 010405 organic chemistry, Chemistry, Organic Chemistry, Glutathione, Kinetin, In vitro, 0104 chemical sciences, 3. Good health, 010404 medicinal & biomolecular chemistry, Oxidative Stress, Mechanism of action, Cytoprotection, Purines, Molecular Medicine, medicine.symptom, Oxidative stress |
| الوصف: | Kinetin (N6-furfuryladenine), a plant growth substance of the cytokinin family, has been shown to modulate aging and various age-related conditions in animal models. Here we report the synthesis of kinetin isosteres with the purine ring replaced by other bicyclic heterocycles, and the biological evaluation of their activity in several in vitro models related to neurodegenerative diseases. Our findings indicate that kinetin isosteres protect Friedreich́s ataxia patient-derived fibroblasts against glutathione depletion, protect neuron-like SH-SY5Y cells from glutamate-induced oxidative damage, and correct aberrant splicing of the ELP1 gene in fibroblasts derived from a familial dysautonomia patient. Although the mechanism of action of kinetin derivatives remains unclear, our data suggest that the cytoprotective activity of some purine isosteres is mediated by their ability to reduce oxidative stress. Further, the studies of permeation across artificial membrane and model gut and blood-brain barriers indicate that the compounds are orally available and can reach central nervous system. Overall, our data demonstrate that isosteric replacement of the kinetin purine scaffold is a fruitful strategy for improving known biological activities of kinetin and discovering novel therapeutic opportunities. |
| تدمد: | 1464-3391 0968-0896 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ecd9c8d687881f84bf5a1fe1e68f285b https://pubmed.ncbi.nlm.nih.gov/33497938 |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi.dedup.....ecd9c8d687881f84bf5a1fe1e68f285b |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14643391 09680896 |
|---|