{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T16:24:40Z","timestamp":1790785480212,"version":"4.1.0"},"reference-count":37,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,18]],"date-time":"2023-01-18T00:00:00Z","timestamp":1674000000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"inistry of Education, Culture, Sports, Science, and Technology, Japan","doi-asserted-by":"publisher","award":["22K06508"],"award-info":[{"award-number":["22K06508"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>In diseases related to oxidative stress, accumulation of metal ions at the site of pathogenesis results in the generation of reactive oxygen species (ROS) through the reductive activation of oxygen molecules catalyzed by the metal ions. If these metals can be removed and the generated ROS can be strongly scavenged, such diseases can be prevented and treated. Planar catechins exhibit stronger radical scavenging activity than natural catechins and can efficiently scavenge hydroxyl radicals generated by the Fenton reaction without showing pro-oxidant effects, even in the presence of iron ions. Hence, in the current study, we designed a compound in which diethylenetriaminepentaacetic acid (DTPA), a metal chelator, was bound to a planar catechin with enhanced radical scavenging activity by immobilizing the steric structure of a natural catechin to be planar. This compound showed almost no radical scavenging activity due to intramolecular hydrogen bonding of DTPA with the planar catechins; however, when coordinated with Fe3+, it showed more potent radical scavenging activity than planar catechins. Owing to its potent antioxidant activity triggered by metal coordination and its inhibition of ROS generation by trapping metal ions, this compound might exert excellent preventive and therapeutic effects against oxidative stress-related diseases.<\/jats:p>","DOI":"10.3390\/antiox12020225","type":"journal-article","created":{"date-parts":[[2023,1,19]],"date-time":"2023-01-19T02:51:37Z","timestamp":1674096697000},"page":"225","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["DTPA-Bound Planar Catechin with Potent Antioxidant Activity Triggered by Fe3+ Coordination"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9677-7911","authenticated-orcid":false,"given":"Kiyoshi","family":"Fukuhara","sequence":"first","affiliation":[{"name":"Division of Organic and Medicinal Chemistry, School of Pharmacy, Showa University, Shinagawa-ku, Tokyo 142-8555, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9204-0664","authenticated-orcid":false,"given":"Ikuo","family":"Nakanishi","sequence":"additional","affiliation":[{"name":"Quantum RedOx Chemistry Team, Institute for Quantum Life Science (iQLS), Quantum Life and Medical Science Directorate, National Institutes for Quantum Science and Technology (QST), Inage-ku, Chiba 263-8555, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kohei","family":"Imai","sequence":"additional","affiliation":[{"name":"Division of Organic and Medicinal Chemistry, School of Pharmacy, Showa University, Shinagawa-ku, Tokyo 142-8555, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirei","family":"Mizuno","sequence":"additional","affiliation":[{"name":"Division of Organic and Medicinal Chemistry, School of Pharmacy, Showa University, Shinagawa-ku, Tokyo 142-8555, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8151-4067","authenticated-orcid":false,"given":"Ken-ichiro","family":"Matsumoto","sequence":"additional","affiliation":[{"name":"Quantitative RedOx Sensing Group, Department of Radiation Regulatory Science Research, National Institute of Radiological Sciences (NIRS), Quantum Life and Medical Science Directorate, National Institutes for Quantum Science and Technology (QST), Inage-ku, Chiba 263-8555, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akiko","family":"Ohno","sequence":"additional","affiliation":[{"name":"Division of Risk Assessment, Center for Biological Safety & Research, National Institute of Health Sciences, Kawasaki-ku, Kawasaki, Kanagawa, Yokohama 210-9501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Hajam, Y.A., Rani, R., Ganie, S.Y., Sheikh, T.A., Javaid, D., Qadri, S.S., Pramodh, S., Alsulimani, A., Alkhanani, M.F., and Harakeh, S. (2022). Oxidative Stress in Human Pathology and Aging: Molecular Mechanisms and Perspectives. Cells, 11.","DOI":"10.3390\/cells11030552"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Leyane, T.S., Jere, S.W., and Houreld, N.N. (2022). Oxidative Stress in Ageing and Chronic Degenerative Pathologies: Molecular Mechanisms Involved in Counteracting Oxidative Stress and Chronic Inflammation. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23137273"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/j.pharma.2021.11.004","article-title":"Interweaving of reactive oxygen species and major neurological and psychiatric disorders","volume":"80","author":"Umare","year":"2022","journal-title":"Ann. Pharm. Fran\u00e7aises"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Teleanu, D.M., Niculescu, A.G., Lungu, I.I., Radu, C.I., Vlad\u00e2cenco, O., Roza, E., Cost\u0103chescu, B., Grumezescu, A.M., and Teleanu, R.I. (2022). An Overview of Oxidative Stress, Neuroinflammation, and Neurodegenerative Diseases. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23115938"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"7743705","DOI":"10.1155\/2022\/7743705","article-title":"Perspectives on the Molecular Mediators of Oxidative Stress and Antioxidant Strategies in the Context of Neuroprotection and Neurolongevity: An Extensive Review","volume":"2022","author":"Shohag","year":"2022","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1016\/j.freeradbiomed.2011.05.017","article-title":"Vitamins C and E: Beneficial effects from a mechanistic perspective","volume":"51","author":"Traber","year":"2011","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.freeradbiomed.2015.03.018","article-title":"Influence of vitamin C and vitamin E on redox signaling: Implications for exercise adaptations","volume":"84","author":"Cobley","year":"2015","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1111\/jnc.15442","article-title":"Too much for your own good: Excessive dopamine damages neurons and contributes to Parkinson\u2019s disease: An Editorial Highlight for \u201cEnhanced tyrosine hydroxylase activity induces oxidative stress, causes accumulation of autotoxic catecholamine metabolites, and augments amphetamine effects in vivo\u201d","volume":"158","author":"Masato","year":"2021","journal-title":"J. Neurochem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.cca.2021.08.009","article-title":"Dopamine in Parkinson\u2019s disease","volume":"522","author":"Latif","year":"2021","journal-title":"Clin. Chim. Acta"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1016\/j.redox.2017.10.014","article-title":"Oxidative stress and the amyloid beta peptide in Alzheimer\u2019s disease","volume":"14","author":"Cheignon","year":"2018","journal-title":"Redox Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1007\/s11011-021-00765-w","article-title":"Role of metals in Alzheimer\u2019s disease","volume":"36","author":"Das","year":"2021","journal-title":"Metab. Brain Dis."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Mor\u00e9n, C., de Souza, R.M., Giraldo, D.M., and Uff, C. (2022). Antioxidant Therapeutic Strategies in Neurodegenerative Diseases. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23169328"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"7934442","DOI":"10.1155\/2022\/7934442","article-title":"Targeting Oxidative Stress Mechanisms to Treat Alzheimer\u2019s and Parkinson\u2019s Disease: A Critical Review","volume":"2022","author":"Aborode","year":"2022","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Leathem, A., Ortiz-Cerda, T., Dennis, J.M., and Witting, P.K. (2022). Evidence for Oxidative Pathways in the Pathogenesis of PD: Are Antioxidants Candidate Drugs to Ameliorate Disease Progression?. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23136923"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Mandil, R., Prakash, A., Rahal, A., Singh, S.P., Sharma, D., Kumar, R., and Garg, S.K. (2020). In vitro and in vivo effects of flubendiamide and copper on cyto-genotoxicity, oxidative stress and spleen histology of rats and its modulation by resveratrol, catechin, curcumin and \u03b1-tocopherol. BMC Pharmacol. Toxicol., 21.","DOI":"10.1186\/s40360-020-00405-6"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Ruhee, R.T., and Suzuki, K. (2020). The Integrative Role of Sulforaphane in Preventing Inflammation, Oxidative Stress and Fatigue: A Review of a Potential Protective Phytochemical. Antioxidants, 9.","DOI":"10.3390\/antiox9060521"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Thiruvengadam, M., Venkidasamy, B., Subramanian, U., Samynathan, R., Ali Shariati, M., Rebezov, M., Girish, S., Thangavel, S., Dhanapal, A.R., and Fedoseeva, N. (2021). Bioactive Compounds in Oxidative Stress-Mediated Diseases: Targeting the NRF2\/ARE Signaling Pathway and Epigenetic Regulation. Antioxidants, 10.","DOI":"10.3390\/antiox10121859"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Speisky, H., Shahidi, F., Costa de Camargo, A., and Fuentes, J. (2022). Revisiting the Oxidation of Flavonoids: Loss, Conservation or Enhancement of Their Antioxidant Properties. Antioxidants, 11.","DOI":"10.3390\/antiox11010133"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"24458","DOI":"10.1007\/s11356-021-17667-0","article-title":"Exploring multifunctional antioxidants as potential agents for management of neurological disorders","volume":"29","author":"Sindhu","year":"2022","journal-title":"Environ. Sci. Pollut. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"521","DOI":"10.3748\/wjg.v25.i5.521","article-title":"Iron and liver fibrosis: Mechanistic and clinical aspects","volume":"25","author":"Mehta","year":"2019","journal-title":"World J. Gastroenterol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Behl, T., Madaan, P., Sehgal, A., Singh, S., Anwer, M.K., Makeen, H.A., Albratty, M., Mohan, S., and Bungau, S. (2022). Mechanistic Insights Expatiating the Redox-Active-Metal-Mediated Neuronal Degeneration in Parkinson\u2019s Disease. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23020678"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.neuro.2021.11.003","article-title":"Mitochondrial iron metabolism and neurodegenerative diseases","volume":"88","author":"Cheng","year":"2022","journal-title":"Neurotoxicology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1016\/S0950-3536(05)80133-7","article-title":"Control of disease by selective iron depletion: A novel therapeutic strategy utilizing iron chelators","volume":"7","author":"Hershko","year":"1994","journal-title":"Bailli\u00e8re\u2019s Clin. Haematol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"175133","DOI":"10.1016\/j.ejphar.2022.175133","article-title":"Therapeutic Insights on Ferroptosis in Parkinson\u2019s disease","volume":"930","author":"Thapa","year":"2022","journal-title":"Eur. J. Pharmacol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1021\/acs.molpharmaceut.0c00474","article-title":"Challenges and Opportunities of Deferoxamine Delivery for Treatment of Alzheimer\u2019s Disease, Parkinson\u2019s Disease, and Intracerebral Hemorrhage","volume":"18","author":"Farr","year":"2021","journal-title":"Mol. Pharm."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.gcb.2009.07.032","article-title":"Hepatic iron overload and risk of hepatocellular carcinoma in cirrhosis","volume":"34","author":"Nahon","year":"2010","journal-title":"Gastroent\u00e9rologie Clin. Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"439","DOI":"10.3390\/v5020439","article-title":"HCV and oxidative stress in the liver","volume":"5","author":"Ivanov","year":"2013","journal-title":"Viruses"},{"key":"ref_28","first-page":"859697","article-title":"Nutrition therapy for liver diseases based on the status of nutritional intake","volume":"2012","author":"Yasutake","year":"2012","journal-title":"Gastroenterol. Res. Pr."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.freeradbiomed.2018.09.044","article-title":"Mitochondrial damage and iron metabolic dysregulation in hepatitis C virus infection","volume":"133","author":"Hino","year":"2019","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1139\/o01-239","article-title":"Cancer prevention by bovine lactoferrin and underlying mechanisms\u2014A review of experimental and clinical studies","volume":"80","author":"Tsuda","year":"2002","journal-title":"Biochem. Cell Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"6524","DOI":"10.1021\/ja057763c","article-title":"Planar catechin analogues with alkyl side chains: A potent antioxidant and an alpha-glucosidase inhibitor","volume":"128","author":"Hakamata","year":"2006","journal-title":"J. Am. Chem. Soc."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"5952","DOI":"10.1021\/ja0178259","article-title":"Enhanced radical-scavenging activity of a planar catechin analogue","volume":"124","author":"Fukuhara","year":"2002","journal-title":"J. Am. Chem. Soc."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/S0014-5793(01)02226-8","article-title":"ESR studies on reaction of saccharide with the free radicals generated from the xanthine oxidase\/hypoxanthine system containing iron","volume":"492","author":"Luo","year":"2001","journal-title":"FEBS Lett."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"855s","DOI":"10.1093\/ajcn\/88.3.855S","article-title":"Role of copper in human neurological disorders","volume":"88","author":"Desai","year":"2008","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2152\/jmi.69.1","article-title":"The role of iron in obesity and diabetes","volume":"69","author":"Ikeda","year":"2022","journal-title":"J. Med. Invest."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"110173","DOI":"10.1016\/j.cbi.2022.110173","article-title":"Essential metals in health and disease","volume":"367","author":"Jomova","year":"2022","journal-title":"Chem. Interactions"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"7944","DOI":"10.1021\/jf070449c","article-title":"A comparative study of the antioxidant power of flavonoid catechin and its planar analogue","volume":"55","author":"Leopoldini","year":"2007","journal-title":"J. Agric. Food Chem."}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/12\/2\/225\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:09:02Z","timestamp":1760119742000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/12\/2\/225"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,18]]},"references-count":37,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["antiox12020225"],"URL":"https:\/\/doi.org\/10.3390\/antiox12020225","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,18]]}}}