{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,19]],"date-time":"2026-04-19T19:06:49Z","timestamp":1776625609387,"version":"3.51.2"},"reference-count":27,"publisher":"Wiley","issue":"18","license":[{"start":{"date-parts":[[2021,6,22]],"date-time":"2021-06-22T00:00:00Z","timestamp":1624320000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemMedChem"],"published-print":{"date-parts":[[2021,9,16]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Dantrolene, a drug used for the management of malignant hyperthermia, had been recently evaluated for prospective repurposing as multitarget agent for neurodegenerative syndromes, including Alzheimer's disease (AD). Herein, twenty\u2010one dantrolene\u2010like hydrazide and hydrazone analogues were synthesized with the aim of exploring structure\u2010activity relationships (SARs) for the inhibition of human monoamine oxidases (MAOs) and acetylcholinesterase (AChE), two well\u2010established target enzymes for anti\u2010AD drugs. With few exceptions, the newly synthesized compounds exhibited selectivity toward MAO\u2005B over either MAO\u2005A or AChE, with the secondary aldimine\u2005<jats:bold>9<\/jats:bold> and phenylhydrazone <jats:bold>20<\/jats:bold> attaining IC<jats:sub>50<\/jats:sub> values of 0.68 and 0.81\u2005\u03bcM, respectively. While no general SAR trend was observed with lipophilicity descriptors, a molecular simplification strategy allowed the main pharmacophore features to be identified, which are responsible for the inhibitory activity toward MAO\u2005B. Finally, further in\u2005vitro investigations revealed cell protection from oxidative insult and activation of carnitine\/acylcarnitine carrier as concomitant biological activities responsible for neuroprotection by hits <jats:bold>9<\/jats:bold> and <jats:bold>20<\/jats:bold> and other promising compounds in the examined series.<\/jats:p>","DOI":"10.1002\/cmdc.202100209","type":"journal-article","created":{"date-parts":[[2021,5,28]],"date-time":"2021-05-28T03:25:05Z","timestamp":1622172305000},"page":"2807-2816","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Synthesis and Biological Evaluation of Dantrolene\u2010Like Hydrazide and Hydrazone Analogues as Multitarget Agents for Neurodegenerative Diseases"],"prefix":"10.1002","volume":"16","author":[{"given":"Isabella","family":"Bolognino","sequence":"first","affiliation":[{"name":"Department of Pharmacy-Pharmaceutical Sciences University of Bari Aldo Moro  Via E. Orabona 4 70125 Bari Italy"},{"name":"Department of Engineering and Applied Sciences University of Bergamo  Viale G. Marconi 5 24044 Dalmine Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicola","family":"Giangregorio","sequence":"additional","affiliation":[{"name":"Institute of Biomembranes Bioenergetics and Molecular Biotechnologies (IBIOM) National Research Council (CNR)  Via Amendola 122\/O 70126 Bari Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annamaria","family":"Tonazzi","sequence":"additional","affiliation":[{"name":"Institute of Biomembranes Bioenergetics and Molecular Biotechnologies (IBIOM) National Research Council (CNR)  Via Amendola 122\/O 70126 Bari Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ant\u00f3n L.","family":"Mart\u00ednez","sequence":"additional","affiliation":[{"name":"BioFarma Research Group Center for Research in Molecular Medicine and Chronic Diseases (CiMUS) University of Santiago de Compostela  Av. Barcelona, Campus Vida 15782 Santiago de Compostela Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cosimo D.","family":"Altomare","sequence":"additional","affiliation":[{"name":"Department of Pharmacy-Pharmaceutical Sciences University of Bari Aldo Moro  Via E. Orabona 4 70125 Bari Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda I.","family":"Loza","sequence":"additional","affiliation":[{"name":"BioFarma Research Group Center for Research in Molecular Medicine and Chronic Diseases (CiMUS) University of Santiago de Compostela  Av. Barcelona, Campus Vida 15782 Santiago de Compostela Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Sablone","sequence":"additional","affiliation":[{"name":"Section of Legal Medicine Interdisciplinary Department of Medicine Bari Policlinico Hospital University of Bari Aldo Moro  Piazza Giulio Cesare 11 70124 Bari Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saverio","family":"Cellamare","sequence":"additional","affiliation":[{"name":"Department of Pharmacy-Pharmaceutical Sciences University of Bari Aldo Moro  Via E. Orabona 4 70125 Bari Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8411-304X","authenticated-orcid":false,"given":"Marco","family":"Catto","sequence":"additional","affiliation":[{"name":"Department of Pharmacy-Pharmaceutical Sciences University of Bari Aldo Moro  Via E. Orabona 4 70125 Bari Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,6,22]]},"reference":[{"key":"e_1_2_7_1_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules24234298"},{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40263-013-0097-3"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.13651"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm00317a011"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2017.02.008"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2019.05.004"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbdv.200690017"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12640-019-0001-0"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/ardp.201200007"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1527-3458.2002.tb00229.x"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2013.01.006"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.2174\/138955751505150408142032"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrestox.5b00050"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules25040820"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2013.08.003"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbabio.2017.04.002"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2015.10.005"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2020.115891"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/ardp.201500352"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2020.115104"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2016.01.040"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.2174\/157018008783928472"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2018.10.016"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2017.08.004"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/0076-6879(95)60150-3"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11010-016-2881-0"},{"key":"e_1_2_7_27_1","unstructured":"EC50Calculator. Available online:https:\/\/www.aatbio.com\/tools\/ec50-calculator\/(accessed on 23 October 2019)."}],"container-title":["ChemMedChem"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cmdc.202100209","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cmdc.202100209","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cmdc.202100209","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T18:06:26Z","timestamp":1760292386000},"score":1,"resource":{"primary":{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/10.1002\/cmdc.202100209"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,22]]},"references-count":27,"journal-issue":{"issue":"18","published-print":{"date-parts":[[2021,9,16]]}},"alternative-id":["10.1002\/cmdc.202100209"],"URL":"https:\/\/doi.org\/10.1002\/cmdc.202100209","archive":["Portico"],"relation":{},"ISSN":["1860-7179","1860-7187"],"issn-type":[{"value":"1860-7179","type":"print"},{"value":"1860-7187","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,22]]},"assertion":[{"value":"2021-03-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-06-22","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}