Sustainable Synthesis, Antiproliferative and Acetylcholinesterase Inhibition of 1,4- and 1,2-Naphthoquinone Derivatives
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 synthe...
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| Format: | Article |
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MDPI AG
2023-01-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/28/3/1232 |
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| author | Rafaela G. Cabral Gonçalo Viegas Rita Pacheco Ana Catarina Sousa Maria Paula Robalo |
| author_facet | Rafaela G. Cabral Gonçalo Viegas Rita Pacheco Ana Catarina Sousa Maria Paula Robalo |
| author_sort | Rafaela G. Cabral |
| collection | DOAJ |
| description | 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 (<b>3a</b>–<b>f</b>), with the highest cytotoxic potential found for compound <b>4a</b> (EC<sub>50</sub> = 3 μM). The same trend was found for the inhibitory action against acetylcholinesterase, with 1,2-NQ derivatives showing higher inhibition<sub>50µM</sub> than their 1,4-NQ homologues, with <b>4h</b> being the most potent compound (Inhibition<sub>50µM</sub> = 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. |
| first_indexed | 2024-03-11T09:33:46Z |
| format | Article |
| id | doaj.art-da15bf1ce557476684a0272571868d3a |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-11T09:33:46Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-da15bf1ce557476684a0272571868d3a2023-11-16T17:29:31ZengMDPI AGMolecules1420-30492023-01-01283123210.3390/molecules28031232Sustainable Synthesis, Antiproliferative and Acetylcholinesterase Inhibition of 1,4- and 1,2-Naphthoquinone DerivativesRafaela G. Cabral0Gonçalo Viegas1Rita Pacheco2Ana Catarina Sousa3Maria Paula Robalo4Departamento de Engenharia Química, Instituto Superior de Engenharia de Lisboa, Instituto Politécnico de Lisboa, 1959-007 Lisboa, PortugalDepartamento de Engenharia Química, Instituto Superior de Engenharia de Lisboa, Instituto Politécnico de Lisboa, 1959-007 Lisboa, PortugalDepartamento de Engenharia Química, Instituto Superior de Engenharia de Lisboa, Instituto Politécnico de Lisboa, 1959-007 Lisboa, PortugalDepartamento de Engenharia Química, Instituto Superior de Engenharia de Lisboa, Instituto Politécnico de Lisboa, 1959-007 Lisboa, PortugalDepartamento de Engenharia Química, Instituto Superior de Engenharia de Lisboa, Instituto Politécnico de Lisboa, 1959-007 Lisboa, PortugalThis 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 (<b>3a</b>–<b>f</b>), with the highest cytotoxic potential found for compound <b>4a</b> (EC<sub>50</sub> = 3 μM). The same trend was found for the inhibitory action against acetylcholinesterase, with 1,2-NQ derivatives showing higher inhibition<sub>50µM</sub> than their 1,4-NQ homologues, with <b>4h</b> being the most potent compound (Inhibition<sub>50µM</sub> = 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.https://www.mdpi.com/1420-3049/28/3/1232naphthoquinoneselectrochemistry behavioracetylcholinesterase inhibitory activitycytotoxic activitybiological activity |
| spellingShingle | Rafaela G. Cabral Gonçalo Viegas Rita Pacheco Ana Catarina Sousa Maria Paula Robalo Sustainable Synthesis, Antiproliferative and Acetylcholinesterase Inhibition of 1,4- and 1,2-Naphthoquinone Derivatives Molecules naphthoquinones electrochemistry behavior acetylcholinesterase inhibitory activity cytotoxic activity biological activity |
| title | Sustainable Synthesis, Antiproliferative and Acetylcholinesterase Inhibition of 1,4- and 1,2-Naphthoquinone Derivatives |
| title_full | Sustainable Synthesis, Antiproliferative and Acetylcholinesterase Inhibition of 1,4- and 1,2-Naphthoquinone Derivatives |
| title_fullStr | Sustainable Synthesis, Antiproliferative and Acetylcholinesterase Inhibition of 1,4- and 1,2-Naphthoquinone Derivatives |
| title_full_unstemmed | Sustainable Synthesis, Antiproliferative and Acetylcholinesterase Inhibition of 1,4- and 1,2-Naphthoquinone Derivatives |
| title_short | Sustainable Synthesis, Antiproliferative and Acetylcholinesterase Inhibition of 1,4- and 1,2-Naphthoquinone Derivatives |
| title_sort | sustainable synthesis antiproliferative and acetylcholinesterase inhibition of 1 4 and 1 2 naphthoquinone derivatives |
| topic | naphthoquinones electrochemistry behavior acetylcholinesterase inhibitory activity cytotoxic activity biological activity |
| url | https://www.mdpi.com/1420-3049/28/3/1232 |
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