{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T01:27:35Z","timestamp":1773019655900,"version":"3.50.1"},"reference-count":58,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,5,24]],"date-time":"2024-05-24T00:00:00Z","timestamp":1716508800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100013209","name":"Hellenic Foundation for Research and Innovation (H.F.R.I.)","doi-asserted-by":"publisher","award":["16"],"award-info":[{"award-number":["16"]}],"id":[{"id":"10.13039\/501100013209","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>A versatile family of quaternary propargylamines was synthesized employing the KA2 multicomponent reaction, through the single-step coupling of a number of amines, ketones, and terminal alkynes. Sustainable synthetic procedures using transition metal catalysts were employed in all cases. The inhibitory activity of these molecules was evaluated against human monoaminoxidase (hMAO)-A and hMAO-B enzymes and was found to be significant. The IC50 values for hMAO-B range from 152.1 to 164.7 nM while the IC50 values for hMAO-A range from 765.6 to 861.6 nM. Furthermore, these compounds comply with Lipinski\u2019s rule of five and exhibit no predicted toxicity. To understand their binding properties with the two target enzymes, key interactions were studied using molecular docking, all-atom molecular dynamics (MD) simulations, and MM\/GBSA binding free energy calculations. Overall, herein, the reported family of propargylamines exhibits promise as potential treatments for neurodegenerative disorders, such as Parkinson\u2019s disease. Interestingly, this is the first time a propargylamine scaffold bearing an internal alkyne has been reported to show activity against monoaminoxidases.<\/jats:p>","DOI":"10.3390\/molecules29112486","type":"journal-article","created":{"date-parts":[[2024,5,24]],"date-time":"2024-05-24T11:17:52Z","timestamp":1716549472000},"page":"2486","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Are Terminal Alkynes Necessary for MAO-A\/MAO-B Inhibition? A New Scaffold Is Revealed"],"prefix":"10.3390","volume":"29","author":[{"given":"Panagiou","family":"Mavroeidi","sequence":"first","affiliation":[{"name":"Laboratory of Organic Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, 15771 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1447-4146","authenticated-orcid":false,"given":"Leandros P.","family":"Zorba","sequence":"additional","affiliation":[{"name":"Laboratory of Organic Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, 15771 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nikolaos V.","family":"Tzouras","sequence":"additional","affiliation":[{"name":"Laboratory of Organic Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, 15771 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6083-1872","authenticated-orcid":false,"given":"Stavros P.","family":"Neofotistos","sequence":"additional","affiliation":[{"name":"Laboratory of Organic Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, 15771 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nikitas","family":"Georgiou","sequence":"additional","affiliation":[{"name":"Laboratory of Organic Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, 15771 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kader","family":"Sahin","sequence":"additional","affiliation":[{"name":"Department of Analytical Chemistry, School of Pharmacy, Bahcesehir University, 34349 Istanbul, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Murat","family":"\u015eent\u00fcrk","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Pharmacy, Agri Ibrahim Cecen University, 04100 Agri, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Serdar","family":"Durdagi","sequence":"additional","affiliation":[{"name":"Molecular Therapy Laboratory, Department of Pharmaceutical Chemistry, School of Pharmacy, Bahcesehir University, 34349 Istanbul, Turkey"},{"name":"Computational Biology and Molecular Simulations Laboratory, Department of Biophysics, School of Medicine, Bahcesehir University, 34349 Istanbul, Turkey"},{"name":"Laboratory for Innovative Drugs (Lab4IND), Computational Drug Design Center (H\u0130TMER), Bahcesehir University, 34349 Istanbul, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4620-5859","authenticated-orcid":false,"given":"Georgios C.","family":"Vougioukalakis","sequence":"additional","affiliation":[{"name":"Laboratory of Organic Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, 15771 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5309-992X","authenticated-orcid":false,"given":"Thomas","family":"Mavromoustakos","sequence":"additional","affiliation":[{"name":"Laboratory of Organic Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, 15771 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"14091","DOI":"10.1021\/acs.chemrev.7b00343","article-title":"Synthesis and Reactivity of Propargylamines in Organic Chemistry","volume":"117","author":"Lauder","year":"2017","journal-title":"Chem. 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