{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T02:57:10Z","timestamp":1783652230508,"version":"3.55.0"},"reference-count":111,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,10,12]],"date-time":"2021-10-12T00:00:00Z","timestamp":1633996800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2018R1A5A2023127"],"award-info":[{"award-number":["NRF-2018R1A5A2023127"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Monoamine oxidase B (MAO-B) metabolizes dopamine and plays an important role in oxidative stress by altering the redox state of neuronal and glial cells. MAO-B inhibitors are a promising therapeutical approach for Parkinson\u2019s disease (PD). Herein, 24 melatonin analogues (3a\u2013x) were synthesized as novel MAO-B inhibitors with the potential to counteract oxidative stress in neuronal PC12 cells. Structure elucidation, characterization, and purity of the synthesized compounds were performed using 1H-NMR, 13C-NMR, HRMS, and HPLC. At 10 \u00b5M, 12 compounds showed &gt;50% MAO-B inhibition. Among them, compounds 3n, 3r, and 3u\u2013w showed &gt;70% inhibition of MAO-B and IC50 values of 1.41, 0.91, 1.20, 0.66, and 2.41 \u00b5M, respectively. When compared with the modest selectivity index of rasagiline (II, a well-known MAO-B inhibitor, SI &gt; 50), compounds 3n, 3r, 3u, and 3v demonstrated better selectivity indices (SI &gt; 71, 109, 83, and 151, respectively). Furthermore, compounds 3n and 3r exhibited safe neurotoxicity profiles in PC12 cells and reversed 6-OHDA- and rotenone-induced neuronal oxidative stress. Both compounds significantly up-regulated the expression of the anti-oxidant enzyme, heme oxygenase (HO)-1. Treatment with Zn(II)-protoporphyrin IX (ZnPP), a selective HO-1 inhibitor, abolished the neuroprotective effects of the tested compounds, suggesting a critical role of HO-1 up-regulation. Both compounds increased the nuclear translocation of Nrf2, which is a key regulator of the antioxidative response. Taken together, these data show that compounds 3n and 3r could be further exploited for their multi-targeted role in oxidative stress-related PD therapy.<\/jats:p>","DOI":"10.3390\/antiox10101604","type":"journal-article","created":{"date-parts":[[2021,10,13]],"date-time":"2021-10-13T04:51:57Z","timestamp":1634100717000},"page":"1604","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Melatonin Analogues Potently Inhibit MAO-B and Protect PC12 Cells against Oxidative Stress"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7398-6155","authenticated-orcid":false,"given":"Ahmed","family":"Elkamhawy","sequence":"first","affiliation":[{"name":"College of Pharmacy, Dongguk University-Seoul, Goyang 10326, Korea"},{"name":"Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiyu","family":"Woo","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Dongguk University-Seoul, Goyang 10326, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noha A.","family":"Gouda","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Dongguk University-Seoul, Goyang 10326, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jushin","family":"Kim","sequence":"additional","affiliation":[{"name":"Convergence Research Center for Diagnosis, Treatment and Care System of Dementia, Korea Institute of Science and Technology (KIST), Seoul 02792, Korea"},{"name":"Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4882-5621","authenticated-orcid":false,"given":"Hossam","family":"Nada","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Dongguk University-Seoul, Goyang 10326, Korea"},{"name":"Pharmaceutical Chemistry Department, Faculty of Pharmacy, Badr University, Cairo 11829, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun Joo","family":"Roh","sequence":"additional","affiliation":[{"name":"Chemical Kinomics Research Center, Korea Institute of Science and Technology (KIST), Seoul 02792, Korea"},{"name":"Division of Bio-Medical Science & Technology, KIST School, Korea University of Science and Technology, Seoul 02792, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7753-214X","authenticated-orcid":false,"given":"Ki Duk","family":"Park","sequence":"additional","affiliation":[{"name":"Convergence Research Center for Diagnosis, Treatment and Care System of Dementia, Korea Institute of Science and Technology (KIST), Seoul 02792, Korea"},{"name":"Division of Bio-Medical Science & Technology, KIST School, Korea University of Science and Technology, Seoul 02792, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jungsook","family":"Cho","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Dongguk University-Seoul, Goyang 10326, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyeong","family":"Lee","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Dongguk University-Seoul, Goyang 10326, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"461","DOI":"10.3233\/JPD-130230","article-title":"The role of oxidative stress in Parkinson\u2019s disease","volume":"3","author":"Dias","year":"2013","journal-title":"J. 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