{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,21]],"date-time":"2026-06-21T07:09:03Z","timestamp":1782025743733,"version":"3.54.5"},"reference-count":44,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T00:00:00Z","timestamp":1633046400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T00:00:00Z","timestamp":1633046400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T00:00:00Z","timestamp":1633046400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T00:00:00Z","timestamp":1633046400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T00:00:00Z","timestamp":1633046400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T00:00:00Z","timestamp":1633046400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T00:00:00Z","timestamp":1633046400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2018M3A9C8016849"],"award-info":[{"award-number":["NRF-2018M3A9C8016849"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"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"}]},{"DOI":"10.13039\/501100008783","name":"National Research Council of Science and Technology","doi-asserted-by":"publisher","award":["CAP-12-1-KIST"],"award-info":[{"award-number":["CAP-12-1-KIST"]}],"id":[{"id":"10.13039\/501100008783","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009367","name":"Mansoura University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009367","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014188","name":"Ministry of Science and ICT, South Korea","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100014188","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003693","name":"Korea Institute of Science and Technology","doi-asserted-by":"publisher","award":["2E31140"],"award-info":[{"award-number":["2E31140"]}],"id":[{"id":"10.13039\/501100003693","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Bioorganic Chemistry"],"published-print":{"date-parts":[[2021,10]]},"DOI":"10.1016\/j.bioorg.2021.105233","type":"journal-article","created":{"date-parts":[[2021,8,2]],"date-time":"2021-08-02T10:59:36Z","timestamp":1627901976000},"page":"105233","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":15,"special_numbering":"C","title":["Discovery of novel and potent safinamide-based derivatives as highly selective hMAO-B inhibitors for treatment of Parkinson's disease (PD): Design, synthesis, in vitro, in vivo and in silico biological studies"],"prefix":"10.1016","volume":"115","author":[{"given":"Ahmed","family":"Elkamhawy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sora","family":"Paik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jong-Hyun","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyeon Jeong","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed H.E.","family":"Hassan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyeong","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ki Duk","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun Joo","family":"Roh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.bioorg.2021.105233_b0005","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1038\/nature20411","article-title":"Ageing, neurodegeneration and brain rejuvenation","volume":"539","author":"Wyss-Coray","year":"2016","journal-title":"Nature"},{"key":"10.1016\/j.bioorg.2021.105233_b0010","doi-asserted-by":"crossref","first-page":"168","DOI":"10.3389\/fnagi.2015.00168","article-title":"Age-related neurodegenerative disease research needs aging models","volume":"7","author":"Johnson","year":"2015","journal-title":"Front. Aging Neurosci."},{"key":"10.1016\/j.bioorg.2021.105233_b0015","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1016\/j.ejps.2017.04.015","article-title":"Design, synthesis, biological evaluation and molecular modelling of 2-(2-aryloxyphenyl)-1,4-dihydroisoquinolin-3(2H)-ones: A novel class of TSPO ligands modulating amyloid-beta-induced mPTP opening","volume":"104","author":"Elkamhawy","year":"2017","journal-title":"European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences"},{"key":"10.1016\/j.bioorg.2021.105233_b0020","doi-asserted-by":"crossref","first-page":"326","DOI":"10.2174\/1570159X14666151208112754","article-title":"Current Treatment Options for Alzheimer's Disease and Parkinson's Disease Dementia","volume":"14","author":"Szeto","year":"2016","journal-title":"Curr. Neuropharmacol."},{"key":"10.1016\/j.bioorg.2021.105233_b0025","doi-asserted-by":"crossref","first-page":"648740","DOI":"10.1155\/2014\/648740","article-title":"Shared mechanisms of neurodegeneration in Alzheimer's disease and Parkinson's disease","volume":"2014","author":"Xie","year":"2014","journal-title":"Biomed Res. Int."},{"key":"10.1016\/j.bioorg.2021.105233_b0030","doi-asserted-by":"crossref","first-page":"4203","DOI":"10.1021\/acs.jmedchem.8b00357","article-title":"Tight-Binding Inhibition of Human Monoamine Oxidase B by Chromone Analogs: A Kinetic, Crystallographic, and Biological Analysis","volume":"61","author":"Reis","year":"2018","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.bioorg.2021.105233_b0035","doi-asserted-by":"crossref","first-page":"46432","DOI":"10.1074\/jbc.M306378200","article-title":"Oxidative alpha-ketoglutarate dehydrogenase inhibition via subtle elevations in monoamine oxidase B levels results in loss of spare respiratory capacity: implications for Parkinson's disease","volume":"278","author":"Kumar","year":"2003","journal-title":"The Journal of biological chemistry"},{"key":"10.1016\/j.bioorg.2021.105233_b0040","doi-asserted-by":"crossref","first-page":"461","DOI":"10.3233\/JPD-130230","article-title":"The role of oxidative stress in Parkinson's disease","volume":"3","author":"Dias","year":"2013","journal-title":"J. Parkinsons Dis."},{"key":"10.1016\/j.bioorg.2021.105233_b0045","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1038\/nm.3639","article-title":"GABA from reactive astrocytes impairs memory in mouse models of Alzheimer's disease","volume":"20","author":"Jo","year":"2014","journal-title":"Nat. Med."},{"key":"10.1016\/j.bioorg.2021.105233_b0050","doi-asserted-by":"crossref","first-page":"4951","DOI":"10.1113\/jphysiol.2014.278754","article-title":"Glial GABA, synthesized by monoamine oxidase B, mediates tonic inhibition","volume":"592","author":"Yoon","year":"2014","journal-title":"J. Physiol."},{"key":"10.1016\/j.bioorg.2021.105233_b0055","doi-asserted-by":"crossref","first-page":"1533","DOI":"10.3892\/mmr.2014.2040","article-title":"Monoamine oxidase inhibitors: promising therapeutic agents for Alzheimer's disease (Review)","volume":"9","author":"Cai","year":"2014","journal-title":"Mol. Med. Rep."},{"key":"10.1016\/j.bioorg.2021.105233_b0060","first-page":"967","article-title":"Close Correlation of Monoamine Oxidase Activity with Progress of Alzheimer's Disease in Mice","volume":"2","author":"Kim","year":"2016","journal-title":"Observed by in Vivo Two-Photon Imaging, ACS central science"},{"key":"10.1016\/j.bioorg.2021.105233_b0065","article-title":"Different generations of type-B monoamine oxidase inhibitors in Parkinson's disease: from bench to bedside","author":"Alborghetti","year":"2018","journal-title":"Curr. Neuropharmacol."},{"key":"10.1016\/j.bioorg.2021.105233_b0070","doi-asserted-by":"crossref","first-page":"1568","DOI":"10.1080\/14756366.2020.1800666","article-title":"Discovery of N-(1-(3-fluorobenzoyl)-1H-indol-5-yl)pyrazine-2-carboxamide: a novel, selective, and competitive indole-based lead inhibitor for human monoamine oxidase B","volume":"35","author":"Elkamhawy","year":"2020","journal-title":"J. Enzyme Inhib. Med. Chem."},{"key":"10.1016\/j.bioorg.2021.105233_b0075","doi-asserted-by":"crossref","first-page":"eaav0316","DOI":"10.1126\/sciadv.aav0316","article-title":"Newly developed reversible MAO-B inhibitor circumvents the shortcomings of irreversible inhibitors in Alzheimer\u2019s disease","volume":"5","author":"Park","year":"2019","journal-title":"Sci. Adv."},{"key":"10.1016\/j.bioorg.2021.105233_b0080","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1007\/s40263-013-0097-3","article-title":"Current place of monoamine oxidase inhibitors in the treatment of depression","volume":"27","author":"Shulman","year":"2013","journal-title":"CNS drugs"},{"key":"10.1016\/j.bioorg.2021.105233_b0085","doi-asserted-by":"crossref","first-page":"492","DOI":"10.2174\/1386207320666170310121337","article-title":"Therapeutic, Molecular and Computational Aspects of Novel Monoamine Oxidase (MAO) Inhibitors","volume":"20","author":"Ramesh","year":"2017","journal-title":"Comb. Chem. High Throughput Screening"},{"key":"10.1016\/j.bioorg.2021.105233_b0090","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1080\/17460441.2019.1637415","article-title":"Novel approaches to the discovery of selective human monoamine oxidase-B inhibitors: is there room for improvement?","volume":"14","author":"Guglielmi","year":"2019","journal-title":"Expert Opin. Drug Discov."},{"key":"10.1016\/j.bioorg.2021.105233_b0095","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1002\/bdd.1822","article-title":"Effects of ketoconazole treatment on the pharmacokinetics of safinamide and its plasma metabolites in healthy adult subjects","volume":"33","author":"Krosser","year":"2012","journal-title":"Biopharm. Drug Dispos."},{"key":"10.1016\/j.bioorg.2021.105233_b0100","unstructured":"Xadago 50mg film-coated tablets Xadago 100mg film-coated tablets - Summary of Product Characteristics, in: https:\/\/www.medicines.org.uk\/emc\/medicine\/31917."},{"key":"10.1016\/j.bioorg.2021.105233_b0105","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.3233\/JAD-161309","article-title":"Sembragiline in Moderate Alzheimer's Disease: Results of a Randomized, Double-Blind, Placebo-Controlled Phase II Trial (MAyflOwer RoAD)","volume":"58","author":"Nave","year":"2017","journal-title":"Journal of Alzheimer's disease : JAD"},{"key":"10.1016\/j.bioorg.2021.105233_b0110","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1038\/nsb732","article-title":"Structure of human monoamine oxidase B, a drug target for the treatment of neurological disorders","volume":"9","author":"Binda","year":"2002","journal-title":"Nat. Struct. Biol."},{"key":"10.1016\/j.bioorg.2021.105233_b0115","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1515\/BMC.2011.030","article-title":"Structures and Mechanism of the Monoamine Oxidase Family","volume":"2","author":"Gaweska","year":"2011","journal-title":"Biomol. Concepts."},{"key":"10.1016\/j.bioorg.2021.105233_b0120","doi-asserted-by":"crossref","first-page":"4860","DOI":"10.1111\/j.1742-4658.2011.08386.x","article-title":"The 'gating' residues Ile199 and Tyr326 in human monoamine oxidase B function in substrate and inhibitor recognition","volume":"278","author":"Milczek","year":"2011","journal-title":"The FEBS journal"},{"key":"10.1016\/j.bioorg.2021.105233_b0125","doi-asserted-by":"crossref","first-page":"5848","DOI":"10.1021\/jm070677y","article-title":"Structures of human monoamine oxidase B complexes with selective noncovalent inhibitors: safinamide and coumarin analogs","volume":"50","author":"Binda","year":"2007","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.bioorg.2021.105233_b0130","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1159\/000354805","article-title":"Disposition and metabolism of safinamide, a novel drug for Parkinson's disease, in healthy male volunteers","volume":"92","author":"Leuratti","year":"2013","journal-title":"Pharmacology"},{"key":"10.1016\/j.bioorg.2021.105233_b0135","first-page":"622","article-title":"Xadago (Safinamide): A Monoamine Oxidase B Inhibitor for the Adjunct Treatment of Motor Symptoms in Parkinson's Disease","volume":"42","author":"Cruz","year":"2017","journal-title":"P & T"},{"key":"10.1016\/j.bioorg.2021.105233_b0140","first-page":"31","article-title":"Safinamide: an add-on treatment for managing Parkinson's disease","volume":"10","author":"Muller","year":"2018","journal-title":"Clinical pharmacology : advances and applications"},{"key":"10.1016\/j.bioorg.2021.105233_b0145","doi-asserted-by":"crossref","first-page":"3189","DOI":"10.1080\/00397919208021132","article-title":"Iron-Ammonium Chloride - A Convenient and Inexpensive Reductant","volume":"22","author":"Ramadas","year":"1992","journal-title":"Synth. Commun."},{"key":"10.1016\/j.bioorg.2021.105233_b0150","doi-asserted-by":"crossref","first-page":"6486","DOI":"10.1016\/j.bmc.2015.08.012","article-title":"Synthesis of a series of unsaturated ketone derivatives as selective and reversible monoamine oxidase inhibitors","volume":"23","author":"Choi","year":"2015","journal-title":"Bioorg. Med. Chem."},{"key":"10.1016\/j.bioorg.2021.105233_b0155","unstructured":"S. Nishino, H. Shima, H. Oda, S. Suzuki, Selective preparation of 3-halogeno-4-hydrocarbyloxynitrobenzenes from 3,4-dihalogenonitrobenzenes, in, Ube Industries, Ltd., Japan . 2009, pp. 8pp."},{"key":"10.1016\/j.bioorg.2021.105233_b0160","doi-asserted-by":"crossref","first-page":"8546","DOI":"10.1021\/jm100665z","article-title":"Novel Chimeric Histone Deacetylase Inhibitors: A Series of Lapatinib Hybrids as Potent Inhibitors of Epidermal Growth Factor Receptor (EGFR), Human Epidermal Growth Factor Receptor 2 (HER2), and Histone Deacetylase Activity","volume":"53","author":"Mahboobi","year":"2010","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.bioorg.2021.105233_b0165","unstructured":"K.E. Lackey, N. Spector, E.R. Wood, III, W. Xia, 4-Quinazolineamine derivative combination with other antineoplastic agent for cancer treatment, and compound preparation, in, Glaxo Group Limited, UK . 2002, pp. 57 pp."},{"key":"10.1016\/j.bioorg.2021.105233_b0170","series-title":"Preparation of benzyloxy anilide derivatives as potassium channel modulators, in","first-page":"30","author":"Wu","year":"2009"},{"key":"10.1016\/j.bioorg.2021.105233_b0175","series-title":"Preparation of arylaminoheteroaryls as protozoan parasite growth inhibitors, in","first-page":"54","author":"Pollastri","year":"2015"},{"key":"10.1016\/j.bioorg.2021.105233_b0180","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1016\/j.ejmech.2018.06.011","article-title":"Surmounting the resistance against EGFR inhibitors through the development of thieno[2,3-d]pyrimidine-based dual EGFR\/HER2 inhibitors","volume":"155","author":"Milik","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.bioorg.2021.105233_b0185","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1002\/ardp.201600197","article-title":"Design and Synthesis of 4-Anilinothieno[2,3-d]pyrimidine-Based Compounds as Dual EGFR\/HER-2 Inhibitors","volume":"349","author":"Abd El Hadi","year":"2016","journal-title":"Arch. Pharm. (Weinheim, Ger.)"},{"key":"10.1016\/j.bioorg.2021.105233_b0190","series-title":"Preparation of phthalanilate and related compounds as antibacterial agents, in","first-page":"146","author":"Mobashery","year":"2011"},{"key":"10.1016\/j.bioorg.2021.105233_b0195","doi-asserted-by":"crossref","first-page":"4637","DOI":"10.1021\/acs.jmedchem.5b02006","article-title":"Design, Synthesis, and Structure-Activity Relationship Study of Novel Indole-2-carboxamide Derivatives as Anti-inflammatory Agents for the Treatment of Sepsis","volume":"59","author":"Liu","year":"2016","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.bioorg.2021.105233_b0200","unstructured":"D. Zhang, Preparation of phenylquinazolinamine derivatives for use as protein kinases inhibitors, in, Medolution Limited, Peop. Rep. China . 2010, pp. 48pp."},{"key":"10.1016\/j.bioorg.2021.105233_b0205","series-title":"Multi-functional small molecules as anti-proliferative agents and their preparation, in","first-page":"494","author":"Cai","year":"2008"},{"key":"10.1016\/j.bioorg.2021.105233_b0210","doi-asserted-by":"crossref","first-page":"3820","DOI":"10.1021\/jm400349k","article-title":"Kinase Scaffold Repurposing for Neglected Disease Drug Discovery: Discovery of an Efficacious, Lapatanib-Derived Lead Compound for Trypanosomiasis","volume":"56","author":"Patel","year":"2013","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.bioorg.2021.105233_b0215","doi-asserted-by":"crossref","first-page":"1473","DOI":"10.1021\/jm401788m","article-title":"Discovery of Vinyl Sulfones as a Novel Class of Neuroprotective Agents toward Parkinson\u2019s Disease Therapy","volume":"57","author":"Woo","year":"2014","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.bioorg.2021.105233_b0220","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/j.bmc.2017.11.036","article-title":"Synthesis and evaluation of biaryl derivatives for structural characterization of selective monoamine oxidase B inhibitors toward Parkinson's disease therapy","volume":"26","author":"Yeon","year":"2018","journal-title":"Bioorg. Med. Chem."}],"container-title":["Bioorganic Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0045206821006106?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0045206821006106?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T08:30:18Z","timestamp":1758616218000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0045206821006106"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10]]},"references-count":44,"alternative-id":["S0045206821006106"],"URL":"https:\/\/doi.org\/10.1016\/j.bioorg.2021.105233","relation":{},"ISSN":["0045-2068"],"issn-type":[{"value":"0045-2068","type":"print"}],"subject":[],"published":{"date-parts":[[2021,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Discovery of novel and potent safinamide-based derivatives as highly selective hMAO-B inhibitors for treatment of Parkinson's disease (PD): Design, synthesis, in vitro, in vivo and in silico biological studies","name":"articletitle","label":"Article Title"},{"value":"Bioorganic Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.bioorg.2021.105233","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2021 Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"105233"}}