Applied Sciences (Jan 2019)

Synthesis, Biological Evaluation and Docking Studies of Chalcone and Flavone Analogs as Antioxidants and Acetylcholinesterase Inhibitors

  • Laura Díaz-Rubio,
  • Rufina Hernández-Martínez,
  • Arturo Estolano-Cobián,
  • Daniel Chávez-Velasco,
  • Ricardo Salazar-Aranda,
  • Noemí Waksman de Torres,
  • Ignacio A. Rivero,
  • Víctor García-González,
  • Marco A. Ramos,
  • Iván Córdova-Guerrero

DOI
https://doi.org/10.3390/app9030410
Journal volume & issue
Vol. 9, no. 3
p. 410

Abstract

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Several oxidative processes are related to a wide range of human chronic and degenerative diseases, like Alzheimer’s disease, which also has been related to cholinergic processes. Therefore, search for new or improved antioxidant molecules with acetylcholinesterase activity is essential to offer alternative chemotherapeutic agents to support current drug therapies. A series of chalcone (2a⁻2k) and flavone (3a⁻3k) analogs were synthesized, characterized, and evaluated as acetylcholinesterase (AChE) inhibitors, and antioxidant agents using 1,1-diphenyl-2-picrylhydrazyl (DPPH•), 2-2′-azino-bis-(3-ethylbenzothiazoline-6-sulfonate) (ABTS•), and β-carotene/linoleic acid bleaching assay. Compounds more active were 3j and 2k in DPPH with EC50 of 1 × 10−8 and 5.4 × 10−3 μg/mL, respectively; 2g and 3i in ABTS (1.14 × 10−2 and 1.9 × 10−3 μg/mL); 2e, 2f, 3f, 2j, and 3j exceeded the α-tocopherol control in the β-carotene assay (98⁻99% of antioxidant activity). At acetylcholinesterase inhibition assay, flavones were more active than chalcones; the best results were compounds 2d and 3d (IC50 21.5 and 26.8 µg/mL, respectively), suggesting that the presence of the nitro group enhances the inhibitory activity. The docking of these two structures were made to understand their interactions with the AChE receptor. Although further in vivo testing must be performed, our results represent an important step towards the identification of improved antioxidants and acetylcholinesterase inhibitors.

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