{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T05:35:08Z","timestamp":1775280908718,"version":"3.50.1"},"reference-count":51,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,1,27]],"date-time":"2023-01-27T00:00:00Z","timestamp":1674777600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Instituto Polit\u00e9cnico de Lisboa","award":["IPL\/2021\/Naf4Med3D_ISEL"],"award-info":[{"award-number":["IPL\/2021\/Naf4Med3D_ISEL"]}]},{"name":"Instituto Polit\u00e9cnico de Lisboa","award":["UIDB\/00100\/2020"],"award-info":[{"award-number":["UIDB\/00100\/2020"]}]},{"name":"Instituto Polit\u00e9cnico de Lisboa","award":["UIDP\/00100\/2020"],"award-info":[{"award-number":["UIDP\/00100\/2020"]}]},{"name":"Instituto Polit\u00e9cnico de Lisboa","award":["LA\/P\/0056\/2020"],"award-info":[{"award-number":["LA\/P\/0056\/2020"]}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia (FCT)","doi-asserted-by":"publisher","award":["IPL\/2021\/Naf4Med3D_ISEL"],"award-info":[{"award-number":["IPL\/2021\/Naf4Med3D_ISEL"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia (FCT)","doi-asserted-by":"publisher","award":["UIDB\/00100\/2020"],"award-info":[{"award-number":["UIDB\/00100\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia (FCT)","doi-asserted-by":"publisher","award":["UIDP\/00100\/2020"],"award-info":[{"award-number":["UIDP\/00100\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia (FCT)","doi-asserted-by":"publisher","award":["LA\/P\/0056\/2020"],"award-info":[{"award-number":["LA\/P\/0056\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Institute of Molecular Sciences (IMS) Associate Laboratory","award":["IPL\/2021\/Naf4Med3D_ISEL"],"award-info":[{"award-number":["IPL\/2021\/Naf4Med3D_ISEL"]}]},{"name":"Institute of Molecular Sciences (IMS) Associate Laboratory","award":["UIDB\/00100\/2020"],"award-info":[{"award-number":["UIDB\/00100\/2020"]}]},{"name":"Institute of Molecular Sciences (IMS) Associate Laboratory","award":["UIDP\/00100\/2020"],"award-info":[{"award-number":["UIDP\/00100\/2020"]}]},{"name":"Institute of Molecular Sciences (IMS) Associate Laboratory","award":["LA\/P\/0056\/2020"],"award-info":[{"award-number":["LA\/P\/0056\/2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>This work describes the design, sustainable synthesis, evaluation of electrochemical and biological properties against HepG2 cell lines, and AChE enzymes of different substituted derivatives of 1,4- and 1,2-naphthoquinones (NQ). A microwave-assisted protocol was optimized with success for the synthesis of the 2-substituted-1,4-NQ series and extended to the 4-substituted-1,2-NQ family, providing an alternative and more sustainable approach to the synthesis of naphthoquinones. The electrochemical properties were studied by cyclic voltammetry, and the redox potentials related to the molecular structural characteristics and the biological properties. Compounds were tested for their potential anti-cancer activity against a hepatocellular carcinoma cell line, HepG2, using MTT assay, and 1,2-NQ derivatives were found to be more active than their 1,4-NQ homologues (3a\u2013f), with the highest cytotoxic potential found for compound 4a (EC50 = 3 \u03bcM). The same trend was found for the inhibitory action against acetylcholinesterase, with 1,2-NQ derivatives showing higher inhibition50\u00b5M than their 1,4-NQ homologues, with 4h being the most potent compound (Inhibition50\u00b5M = 85%). Docking studies were performed for the 1,2-NQ derivatives with the highest inhibitions, showing dual binding interactions with both CAS and PAS sites, while the less active 1,4-NQ derivatives showed interactions with PAS and the mid-gorge region.<\/jats:p>","DOI":"10.3390\/molecules28031232","type":"journal-article","created":{"date-parts":[[2023,1,30]],"date-time":"2023-01-30T01:33:37Z","timestamp":1675042417000},"page":"1232","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Sustainable Synthesis, Antiproliferative and Acetylcholinesterase Inhibition of 1,4- and 1,2-Naphthoquinone Derivatives"],"prefix":"10.3390","volume":"28","author":[{"given":"Rafaela G.","family":"Cabral","sequence":"first","affiliation":[{"name":"Departamento de Engenharia Qu\u00edmica, Instituto Superior de Engenharia de Lisboa, Instituto Polit\u00e9cnico de Lisboa, 1959-007 Lisboa, Portugal"},{"name":"Centro de Qu\u00edmica Estrutural, Institute of Molecular Sciences, Instituto Superior T\u00e9cnico, Universidade de Lisboa, 1049-001 Lisboa, Portugal"}]},{"given":"Gon\u00e7alo","family":"Viegas","sequence":"additional","affiliation":[{"name":"Departamento de Engenharia Qu\u00edmica, Instituto Superior de Engenharia de Lisboa, Instituto Polit\u00e9cnico de Lisboa, 1959-007 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5192-3006","authenticated-orcid":false,"given":"Rita","family":"Pacheco","sequence":"additional","affiliation":[{"name":"Departamento de Engenharia Qu\u00edmica, Instituto Superior de Engenharia de Lisboa, Instituto Polit\u00e9cnico de Lisboa, 1959-007 Lisboa, Portugal"},{"name":"Centro de Qu\u00edmica Estrutural, Institute of Molecular Sciences, Instituto Superior T\u00e9cnico, Universidade de Lisboa, 1049-001 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6133-7406","authenticated-orcid":false,"given":"Ana Catarina","family":"Sousa","sequence":"additional","affiliation":[{"name":"Departamento de Engenharia Qu\u00edmica, Instituto Superior de Engenharia de Lisboa, Instituto Polit\u00e9cnico de Lisboa, 1959-007 Lisboa, Portugal"},{"name":"Centro de Qu\u00edmica Estrutural, Institute of Molecular Sciences, Instituto Superior T\u00e9cnico, Universidade de Lisboa, 1049-001 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8200-6910","authenticated-orcid":false,"given":"Maria Paula","family":"Robalo","sequence":"additional","affiliation":[{"name":"Departamento de Engenharia Qu\u00edmica, Instituto Superior de Engenharia de Lisboa, Instituto Polit\u00e9cnico de Lisboa, 1959-007 Lisboa, Portugal"},{"name":"Centro de Qu\u00edmica Estrutural, Institute of Molecular Sciences, Instituto Superior T\u00e9cnico, Universidade de Lisboa, 1049-001 Lisboa, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1111\/cbdd.13141","article-title":"Naphthoquinones: A continuing source for discovery of therapeutic antineoplastic agents","volume":"91","year":"2018","journal-title":"Chem. 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