{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T21:59:43Z","timestamp":1777413583876,"version":"3.51.4"},"reference-count":63,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,5,5]],"date-time":"2023-05-05T00:00:00Z","timestamp":1683244800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Portuguese Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia (FCT)","award":["UIDB\/00100\/2020"],"award-info":[{"award-number":["UIDB\/00100\/2020"]}]},{"name":"Portuguese Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia (FCT)","award":["UIDP\/00100\/2020"],"award-info":[{"award-number":["UIDP\/00100\/2020"]}]},{"name":"Portuguese Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia (FCT)","award":["UIDB\/04539\/2020"],"award-info":[{"award-number":["UIDB\/04539\/2020"]}]},{"name":"Portuguese Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia (FCT)","award":["UIDP\/04539\/2020"],"award-info":[{"award-number":["UIDP\/04539\/2020"]}]},{"name":"Portuguese Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia (FCT)","award":["LA\/P\/0058\/2020"],"award-info":[{"award-number":["LA\/P\/0058\/2020"]}]},{"name":"Portuguese Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia (FCT)","award":["PT-OPENSCREEN\u2013NORTE-01-0145-FEDER-085468"],"award-info":[{"award-number":["PT-OPENSCREEN\u2013NORTE-01-0145-FEDER-085468"]}]},{"name":"Portuguese Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia (FCT)","award":["PID2020-114714RB-I00"],"award-info":[{"award-number":["PID2020-114714RB-I00"]}]},{"name":"Spanish Ministry of Science and Innovation","award":["UIDB\/00100\/2020"],"award-info":[{"award-number":["UIDB\/00100\/2020"]}]},{"name":"Spanish Ministry of Science and Innovation","award":["UIDP\/00100\/2020"],"award-info":[{"award-number":["UIDP\/00100\/2020"]}]},{"name":"Spanish Ministry of Science and Innovation","award":["UIDB\/04539\/2020"],"award-info":[{"award-number":["UIDB\/04539\/2020"]}]},{"name":"Spanish Ministry of Science and Innovation","award":["UIDP\/04539\/2020"],"award-info":[{"award-number":["UIDP\/04539\/2020"]}]},{"name":"Spanish Ministry of Science and Innovation","award":["LA\/P\/0058\/2020"],"award-info":[{"award-number":["LA\/P\/0058\/2020"]}]},{"name":"Spanish Ministry of Science and Innovation","award":["PT-OPENSCREEN\u2013NORTE-01-0145-FEDER-085468"],"award-info":[{"award-number":["PT-OPENSCREEN\u2013NORTE-01-0145-FEDER-085468"]}]},{"name":"Spanish Ministry of Science and Innovation","award":["PID2020-114714RB-I00"],"award-info":[{"award-number":["PID2020-114714RB-I00"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>With the goal of combating the multi-faceted Alzheimer\u2019s disease (AD), a series of Rivastigmine-Benzimidazole (RIV\u2013BIM) hybrids was recently reported by us as multitarget-directed ligands, thanks to their capacity to tackle important hallmarks of AD. In particular, they exhibited antioxidant activity, acted as cholinesterase inhibitors, and inhibited amyloid-\u03b2 (A\u03b2) aggregation. Herein, we moved forward in this project, studying their ability to chelate redox-active biometal ions, Cu(II) and Fe(III), with widely recognized roles in the generation of oxidative reactive species and in protein misfolding and aggregation in both AD and Parkinson\u2019s disease (PD). Although Cu(II) chelation showed higher efficiency for the positional isomers of series 5 than those of series 4 of the hybrids, the A\u03b2-aggregation inhibition appears more dependent on their capacity for fibril intercalation than on copper chelation. Since monoamine oxidases (MAOs) are also important targets for the treatment of AD and PD, the capacity of these hybrids to inhibit MAO-A and MAO-B was evaluated, and they showed higher activity and selectivity for MAO-A. The rationalization of the experimental evaluations (metal chelation and MAO inhibition) was supported by computational molecular modeling studies. Finally, some compounds showed also neuroprotective effects in human neuroblastoma (SH-SY5Y cells) upon treatment with 1-methyl-4-phenylpyridinium (MPP+), a neurotoxic metabolite of a Parkinsonian-inducing agent.<\/jats:p>","DOI":"10.3390\/ijms24098312","type":"journal-article","created":{"date-parts":[[2023,5,5]],"date-time":"2023-05-05T09:18:09Z","timestamp":1683278289000},"page":"8312","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Rivastigmine\u2013Benzimidazole Hybrids as Promising Multitarget Metal-Modulating Compounds for Potential Treatment of Neurodegenerative Diseases"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8946-2858","authenticated-orcid":false,"given":"David","family":"Vicente-Zurdo","sequence":"first","affiliation":[{"name":"Centro de Qu\u00edmica Estrutural, Departamento de Engenharia Qu\u00edmica, Institute of Molecular Sciences, Instituto Superior T\u00e9cnico, Universidade de Lisboa, Av. Rovisco Pais 1, 1049-001 Lisboa, Portugal"},{"name":"Department of Analytical Chemistry, Faculty of Chemistry, Complutense University of Madrid, Avenida Complutense s\/n, 28040 Madrid, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7787-6639","authenticated-orcid":false,"given":"Leonardo","family":"Brunetti","sequence":"additional","affiliation":[{"name":"Centro de Qu\u00edmica Estrutural, Departamento de Engenharia Qu\u00edmica, Institute of Molecular Sciences, Instituto Superior T\u00e9cnico, Universidade de Lisboa, Av. Rovisco Pais 1, 1049-001 Lisboa, Portugal"},{"name":"Department of Pharmacy-Pharmaceutical Sciences, University of Bari Aldo Moro, via E. Orabona 4, 70125 Bari, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7980-5818","authenticated-orcid":false,"given":"Luca","family":"Piemontese","sequence":"additional","affiliation":[{"name":"Department of Pharmacy-Pharmaceutical Sciences, University of Bari Aldo Moro, via E. Orabona 4, 70125 Bari, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8171-9062","authenticated-orcid":false,"given":"Beatriz","family":"Guedes","sequence":"additional","affiliation":[{"name":"CNC\u2014Center for Neuroscience and Cell Biology, University of Coimbra, 3000-370 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2199-0555","authenticated-orcid":false,"given":"Sandra M.","family":"Cardoso","sequence":"additional","affiliation":[{"name":"CNC\u2014Center for Neuroscience and Cell Biology, University of Coimbra, 3000-370 Coimbra, Portugal"},{"name":"FMUC\u2014Faculty of Medicine, University of Coimbra, 3000-370 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7010-9808","authenticated-orcid":false,"given":"Daniel","family":"Chavarria","sequence":"additional","affiliation":[{"name":"CIQUP-IMS, Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, Rua do Campo Alegre s\/n, 4169-007 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1050-2402","authenticated-orcid":false,"given":"Fernanda","family":"Borges","sequence":"additional","affiliation":[{"name":"CIQUP-IMS, Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, Rua do Campo Alegre s\/n, 4169-007 Porto, Portugal"}]},{"given":"Yolanda","family":"Madrid","sequence":"additional","affiliation":[{"name":"Department of Analytical Chemistry, Faculty of Chemistry, Complutense University of Madrid, Avenida Complutense s\/n, 28040 Madrid, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8554-4992","authenticated-orcid":false,"given":"S\u00edlvia","family":"Chaves","sequence":"additional","affiliation":[{"name":"Centro de Qu\u00edmica Estrutural, Departamento de Engenharia Qu\u00edmica, Institute of Molecular Sciences, Instituto Superior T\u00e9cnico, Universidade de Lisboa, Av. Rovisco Pais 1, 1049-001 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4069-9368","authenticated-orcid":false,"given":"M. Am\u00e9lia","family":"Santos","sequence":"additional","affiliation":[{"name":"Centro de Qu\u00edmica Estrutural, Departamento de Engenharia Qu\u00edmica, Institute of Molecular Sciences, Instituto Superior T\u00e9cnico, Universidade de Lisboa, Av. Rovisco Pais 1, 1049-001 Lisboa, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,5]]},"reference":[{"key":"ref_1","unstructured":"Alzheimer\u2019s Association (2021). Alzheimer\u2019s disease facts and figures. 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