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This study involves the isolation of lignans, including phyllanthin, hypophyllanthin, and nirtetraline, from\n                    <jats:italic>Phyllanthus amarus<\/jats:italic>\n                    . Furthermore, the phyllanhtin was semi\u2010synthetically modified to give phyllanthin oxadiazole derivatives and was evaluated for neuroprotective activity in scopolamine\u2010injured neuroblastoma\u20102a (N2A) cells. The biochemical assay for reactive oxygen generation (ROS) production in N2A cells was carried out using 2\u2032,7\u2032\u2010dichlorodihydrofluorescein diacetate (DCFDA) dye, and the mitochondrial membrane potential (MMP) was determined in N2A cells by using JC\u20101 dye. Furthermore, the N2A neuronal deaths were evaluated using acridine orange (AO), ethidium bromide (EtBr), and propidium iodide dyes. Among them, nirtetraline, hypophyllanthin, phyllanthin, and compounds\n                    <jats:bold>21<\/jats:bold>\n                    and\n                    <jats:bold>31<\/jats:bold>\n                    showed potential neuroprotective effects in N2A cells against scopolamine\u2010induced neurotoxicity by inhibiting ROS production and improving MMP. Moreover, the synthesized compounds were nontoxic to the N2A cell line. Furthermore, in silico docking studies predicted phyllanthin derivatives\n                    <jats:bold>21<\/jats:bold>\n                    and\n                    <jats:bold>31<\/jats:bold>\n                    exhibit neuroprotective activity by binding to the human NADPH\u2010oxidase 5 enzyme. Thus, compounds\n                    <jats:bold>21<\/jats:bold>\n                    and\n                    <jats:bold>31<\/jats:bold>\n                    can be considered potential neuroprotective leads.\n                  <\/jats:p>","DOI":"10.1002\/ardp.70115","type":"journal-article","created":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T04:27:14Z","timestamp":1760156834000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Semi\u2010Synthesis and Biological Evaluation of Phyllanthin Derivatives as Potential Neuroprotective Agents"],"prefix":"10.1002","volume":"358","author":[{"given":"Bylapudi Lalitha","family":"Kumari","sequence":"first","affiliation":[{"name":"Department of Natural Products, Chemical Sciences National Institute of Pharmaceutical Education and Research\u2010Hyderabad Hyderabad Balanagar India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rahul","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences National Institute of Pharmaceutical Education and Research\u2010Hyderabad Hyderabad Balanagar India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kakade Aditi","family":"Sakharam","sequence":"additional","affiliation":[{"name":"Department of Natural Products, Chemical Sciences National Institute of Pharmaceutical Education and Research\u2010Hyderabad Hyderabad Balanagar India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rutuja","family":"Damare","sequence":"additional","affiliation":[{"name":"Department of Natural Products, Chemical Sciences National Institute of Pharmaceutical Education and Research\u2010Hyderabad Hyderabad Balanagar India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shashi Bala","family":"Singh","sequence":"additional","affiliation":[{"name":"Dr. B.R. 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