Evaluation of the Antioxidant and Neuroprotectant Activities of New Asymmetrical 1,3-Diketones
A series of fourteen new asymmetrical 1,3-diketone derivatives have been synthesized and evaluated in the ABTS, FRAP and DPPH assays as a new chemotype with antioxidant and drug-like properties. All the compounds displayed low cytotoxicity in comparison to curcumin against the human neuroblastoma SH...
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doaj-16d70279e5024799a36d43d714ddb0592020-11-25T02:36:06ZengMDPI AGMolecules1420-30492018-07-01238183710.3390/molecules23081837molecules23081837Evaluation of the Antioxidant and Neuroprotectant Activities of New Asymmetrical 1,3-DiketonesCarla I. Nieto0María Pilar Cornago1María Pilar Cabildo2Dionisia Sanz3Rosa M. Claramunt4María Carmen Torralba5María Rosario Torres6Diana Martínez Casanova7Yaiza Rebeca Sánchez-Alegre8Esther Escudero9José Luis Lavandera10Departamento de Química Orgánica y Bio-Orgánica, Facultad de Ciencias, Universidad Nacional de Educación a distancia (UNED), Paseo Senda del Rey 9, E-28040 Madrid, SpainDepartamento de Química Orgánica y Bio-Orgánica, Facultad de Ciencias, Universidad Nacional de Educación a distancia (UNED), Paseo Senda del Rey 9, E-28040 Madrid, SpainDepartamento de Química Orgánica y Bio-Orgánica, Facultad de Ciencias, Universidad Nacional de Educación a distancia (UNED), Paseo Senda del Rey 9, E-28040 Madrid, SpainDepartamento de Química Orgánica y Bio-Orgánica, Facultad de Ciencias, Universidad Nacional de Educación a distancia (UNED), Paseo Senda del Rey 9, E-28040 Madrid, SpainDepartamento de Química Orgánica y Bio-Orgánica, Facultad de Ciencias, Universidad Nacional de Educación a distancia (UNED), Paseo Senda del Rey 9, E-28040 Madrid, SpainDepartamento de Química Inorgánica I and CAI de Difracción de Rayos-X, Facultad de Ciencias Químicas, Universidad Complutense de Madrid (UCM), E-28040 Madrid, SpainDepartamento de Química Inorgánica I and CAI de Difracción de Rayos-X, Facultad de Ciencias Químicas, Universidad Complutense de Madrid (UCM), E-28040 Madrid, SpainInstituto de Medicina Molecular Aplicada (IMMA), Facultad de Medicina, Universidad CEU San Pablo, Campus de Montepríncipe, Boadilla, E-28668 Madrid, SpainInstituto de Medicina Molecular Aplicada (IMMA), Facultad de Medicina, Universidad CEU San Pablo, Campus de Montepríncipe, Boadilla, E-28668 Madrid, SpainInstituto de Medicina Molecular Aplicada (IMMA), Facultad de Medicina, Universidad CEU San Pablo, Campus de Montepríncipe, Boadilla, E-28668 Madrid, SpainInstituto de Medicina Molecular Aplicada (IMMA), Facultad de Medicina, Universidad CEU San Pablo, Campus de Montepríncipe, Boadilla, E-28668 Madrid, SpainA series of fourteen new asymmetrical 1,3-diketone derivatives have been synthesized and evaluated in the ABTS, FRAP and DPPH assays as a new chemotype with antioxidant and drug-like properties. All the compounds displayed low cytotoxicity in comparison to curcumin against the human neuroblastoma SH-SY5Y cell line. Among them, (3Z,5E)-6-(2,5-difluoro-4-hydroxy-phenyl)-1,1,1-trifluoro-4-hydroxyhexa-3,5-dien-2-one (6b) and (3Z,5E)-6-(2,3-difluoro-4-hydroxy-phenyl)-1,1,1-trifluoro-4-hydroxyhexa-3,5-dien-2-one (7b) with excellent solubility and chemical stability in biorelevant media, have also shown a similar Fe+2 chelation behavior to that of curcumin. Additionally, both derivatives 6b and 7b have afforded good neuroprotection activity against H2O2 induced oxidative stress in the same neuronal cell line, with a significant reduction of intracellular ROS levels, in parallel with a good recovery of the Mitochondrial Membrane Potential (ΔΨm). Compounds 6b and 7b with a promising antioxidant and drug-like profile, with low cytotoxic and good neuroprotectant activity, constitute a new interesting chemical class with high potential as new therapeutic agents against neurodegenerative diseases.http://www.mdpi.com/1420-3049/23/8/1837neurodegenerationoxidative stressneuroprotectantantioxidantβ-diketonesdrug-like properties |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Carla I. Nieto María Pilar Cornago María Pilar Cabildo Dionisia Sanz Rosa M. Claramunt María Carmen Torralba María Rosario Torres Diana Martínez Casanova Yaiza Rebeca Sánchez-Alegre Esther Escudero José Luis Lavandera |
spellingShingle |
Carla I. Nieto María Pilar Cornago María Pilar Cabildo Dionisia Sanz Rosa M. Claramunt María Carmen Torralba María Rosario Torres Diana Martínez Casanova Yaiza Rebeca Sánchez-Alegre Esther Escudero José Luis Lavandera Evaluation of the Antioxidant and Neuroprotectant Activities of New Asymmetrical 1,3-Diketones Molecules neurodegeneration oxidative stress neuroprotectant antioxidant β-diketones drug-like properties |
author_facet |
Carla I. Nieto María Pilar Cornago María Pilar Cabildo Dionisia Sanz Rosa M. Claramunt María Carmen Torralba María Rosario Torres Diana Martínez Casanova Yaiza Rebeca Sánchez-Alegre Esther Escudero José Luis Lavandera |
author_sort |
Carla I. Nieto |
title |
Evaluation of the Antioxidant and Neuroprotectant Activities of New Asymmetrical 1,3-Diketones |
title_short |
Evaluation of the Antioxidant and Neuroprotectant Activities of New Asymmetrical 1,3-Diketones |
title_full |
Evaluation of the Antioxidant and Neuroprotectant Activities of New Asymmetrical 1,3-Diketones |
title_fullStr |
Evaluation of the Antioxidant and Neuroprotectant Activities of New Asymmetrical 1,3-Diketones |
title_full_unstemmed |
Evaluation of the Antioxidant and Neuroprotectant Activities of New Asymmetrical 1,3-Diketones |
title_sort |
evaluation of the antioxidant and neuroprotectant activities of new asymmetrical 1,3-diketones |
publisher |
MDPI AG |
series |
Molecules |
issn |
1420-3049 |
publishDate |
2018-07-01 |
description |
A series of fourteen new asymmetrical 1,3-diketone derivatives have been synthesized and evaluated in the ABTS, FRAP and DPPH assays as a new chemotype with antioxidant and drug-like properties. All the compounds displayed low cytotoxicity in comparison to curcumin against the human neuroblastoma SH-SY5Y cell line. Among them, (3Z,5E)-6-(2,5-difluoro-4-hydroxy-phenyl)-1,1,1-trifluoro-4-hydroxyhexa-3,5-dien-2-one (6b) and (3Z,5E)-6-(2,3-difluoro-4-hydroxy-phenyl)-1,1,1-trifluoro-4-hydroxyhexa-3,5-dien-2-one (7b) with excellent solubility and chemical stability in biorelevant media, have also shown a similar Fe+2 chelation behavior to that of curcumin. Additionally, both derivatives 6b and 7b have afforded good neuroprotection activity against H2O2 induced oxidative stress in the same neuronal cell line, with a significant reduction of intracellular ROS levels, in parallel with a good recovery of the Mitochondrial Membrane Potential (ΔΨm). Compounds 6b and 7b with a promising antioxidant and drug-like profile, with low cytotoxic and good neuroprotectant activity, constitute a new interesting chemical class with high potential as new therapeutic agents against neurodegenerative diseases. |
topic |
neurodegeneration oxidative stress neuroprotectant antioxidant β-diketones drug-like properties |
url |
http://www.mdpi.com/1420-3049/23/8/1837 |
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