{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T17:56:00Z","timestamp":1785779760265,"version":"3.56.0"},"reference-count":106,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Oxidative stress is a major driver of chronic disease, making natural polyphenols attractive scaffolds for modulating inflammation, proteostasis, and cell fate. However, green-tea catechins possess a twisted, conformationally flexible flavan-3-ol framework that limits \u03c0-conjugation, phenoxyl-radical stabilization, and productive interactions with biological targets. This review presents a structure-based framework in which conformational planarization serves as a strategy for functional amplification. Preorganization of the A\/C\u2013B inter-ring bond into a nearly coplanar arrangement reduces the conformational entropy penalty (\u2212T\u0394S) upon binding or reaction while extending conjugation, strengthening \u03c0\u2013\u03c0 interactions, and facilitating redox reactions. This review highlights planarized catechin (PCat) architectures, including PCat\u2013DTPA (a lesion-activated metal-responsive antioxidant), PCat\u2013TrOH (a self-regenerating antioxidant network), procyanidin B3\u2013PCat hybrids, and a planar silybin analog, illustrating how planarization and multivalent recognition enhance ROS regulation, inhibit amyloid-\u03b2 aggregation and neurotoxicity, and suppress cancer cell phenotypes. Collectively, these studies establish PCat as a modular platform for the mechanism-informed design of disease-tailored phenolic antioxidants.<\/jats:p>","DOI":"10.3390\/antiox15080964","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T17:26:52Z","timestamp":1785778012000},"page":"964","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Structure-Guided Design of Planarized Catechin Derivatives: Enhancing Antioxidant and Multifaceted Biological Activities for Therapeutic Applications"],"prefix":"10.3390","volume":"15","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, Showa Medical University School of Pharmacy, Shinagawa-ku, Tokyo 142-8555, Japan"},{"name":"Quantum RedOx Chemistry Team, Quantum Life Spin Group, Institute for Quantum Life Science (iQLS), National Institutes for Quantum Science and Technology (QST), Chiba-shi 263-8555, 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, Quantum Life Spin Group, Institute for Quantum Life Science (iQLS), National Institutes for Quantum Science and Technology (QST), Chiba-shi 263-8555, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiromu","family":"Ito","sequence":"additional","affiliation":[{"name":"Quantum RedOx Chemistry Team, Quantum Life Spin Group, Institute for Quantum Life Science (iQLS), National Institutes for Quantum Science and Technology (QST), Chiba-shi 263-8555, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wakana","family":"Shimizu","sequence":"additional","affiliation":[{"name":"Division of Organic and Medicinal Chemistry, Showa Medical University School of Pharmacy, Shinagawa-ku, Tokyo 142-8555, Japan"},{"name":"Quantum RedOx Chemistry Team, Quantum Life Spin Group, Institute for Quantum Life Science (iQLS), National Institutes for Quantum Science and Technology (QST), Chiba-shi 263-8555, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshimi","family":"Shoji","sequence":"additional","affiliation":[{"name":"Quantum RedOx Chemistry Team, Quantum Life Spin Group, Institute for Quantum Life Science (iQLS), National Institutes for Quantum Science and Technology (QST), Chiba-shi 263-8555, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8328-9249","authenticated-orcid":false,"given":"Kei","family":"Ohkubo","sequence":"additional","affiliation":[{"name":"Quantum RedOx Chemistry Team, Quantum Life Spin Group, Institute for Quantum Life Science (iQLS), National Institutes for Quantum Science and Technology (QST), Chiba-shi 263-8555, Japan"},{"name":"Institute for Open and Transdisciplinary Research Initiatives (OTRI), Osaka University, Suita, Osaka 565-0871, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masao","family":"Morita","sequence":"additional","affiliation":[{"name":"Division of Organic and Medicinal Chemistry, Showa Medical University School of Pharmacy, Shinagawa-ku, Tokyo 142-8555, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sakurako","family":"Okada","sequence":"additional","affiliation":[{"name":"Division of Organic and Medicinal Chemistry, Showa Medical University School of Pharmacy, Shinagawa-ku, Tokyo 142-8555, Japan"},{"name":"Quantum RedOx Chemistry Team, Quantum Life Spin Group, Institute for Quantum Life Science (iQLS), National Institutes for Quantum Science and Technology (QST), Chiba-shi 263-8555, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akiko","family":"Ohno","sequence":"additional","affiliation":[{"name":"Division of Genome Safety Science, National Institute of Health Sciences, 3-25-26 Tonomachi, Kawasaki-ku, Kawasaki City 210-9501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1016\/j.arr.2012.10.004","article-title":"Oxidative stress and cancer: An overview","volume":"12","author":"Sosa","year":"2013","journal-title":"Ageing Res. 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