Evaluation of the Antioxidant and Neuroprotectant Activities of New Asymmetrical 1,3-Diketones

• Main Authors: 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
• Format: Article
• Language: English
• Published: MDPI AG 2018-07-01
• Series: Molecules
• Subjects: neurodegeneration; oxidative stress; neuroprotectant; antioxidant; β-diketones; drug-like properties
• Online Access: http://www.mdpi.com/1420-3049/23/8/1837

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.