Old and new inhibitors of quinone reductase 2 |
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| Authors: | Gilles Ferry Sabrina Hecht Sylvie Berger Natacha Moulharat Francis Coge Gérald Guillaumet Véronique Leclerc Saïd Yous Philippe Delagrange Jean A. Boutin |
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| Affiliation: | 1. Pharmacologie moléculaire et Cellulaire, Institut de Recherches Servier, 125, Chemin de Ronde, 78290 Croissy sur Seine, France;2. Université d’Orléans, ICOA, 45067 Orléans, France;3. Laboratoire de Chimie thérapeutique (EA 1043), Faculté de Pharmacie, 59000 Lille, France;4. Département des Sciences Expérimentales, Institut de Recherches Servier, 11, rue des Moulineaux, 92150 Suresnes, France;1. Department of Pharmacy, Tongji Hospital Affiliated Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China;2. School of Pharmacy, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430030, China;3. Hubei Entry-Exit Inspection and Quarantine Bureau, Wuhan 430050, China;1. Department of Medical Pharmacology, K?r?kkale University, K?r?kkale, Turkey;2. Department of Medical Pharmacology, Gazi University, Ankara, Turkey;3. Department of Rational Drug Use and Supply Management, Turkish Medicines and Medical Devices Agency, Ministry of Health, Ankara, Turkey;4. Member of Turkish Academy of Science, Turkey;1. Zhejiang Key Laboratory of Aquatic Germplasm Resources and College of Biological and Environmental Sciences, Zhejiang Wanli University, Ningbo, Zhejiang 315100, China;2. Laboratory for Marine Fisheries Science and Food Production Processes, Qingdao National Laboratory for Marine Science and Technology, Qingdao, 266071, China;3. School of Animal Sciences, Louisiana State University Agricultural Center, Baton Rouge, LA 70803, USA;4. Loyola University, Department of Biological Sciences, New Orleans, LA 70118, USA;1. Université Paris-Saclay, CNRS, BioCIS, 92290, Châtenay-Malabry, France;2. Institut de Chimie des Substances Naturelles, UPR 2301, CNRS, F-91198, Gif sur Yvette, France;3. INSERM, UMR-S1176, University Paris-Saclay, F-94276, Le Kremlin-Bicetre, France;4. Institute for Advanced Biosciences, INSERM U1209, CNRS UMR5309, Université Grenoble Alpes, Grenoble, France |
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| Abstract: | Quinone reductase 2 is a cytosolic enzyme which catalyses the reduction of quinones, such as menadione and coenzymes Q. Despite a relatively close sequence-based resemblance to NAD(P)H:quinone oxidoreductase 1 (QR1), it has many different features. QR2 is the third melatonin binding site (MT3). It is inhibited in the micromolar range by melatonin, and does not accept conventional phosphorylated nicotinamides as hydride donors. QR2 has a powerful capacity to activate quinones leading to unexpected toxicity situations. In the present paper, we report the characterization of three QR2 modulators: melatonin, resveratrol and S29434. The latter compound inhibits QR2 activity with an IC50 in the low nanomolar range. The potency of the modulators ranged as follows, from the least to the most potent: melatonin < resveratrol < S29434. These molecular tools might permit to explore and better understand the relationship existing between QR2 catalytic activity and the various pathological situations in which QR2 has a key role. |
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