Rational Design of Multifunctional Ferulic Acid Derivatives Aimed for Alzheimer's and Parkinson's Diseases
Por:
Guzman-Lopez, Eduardo Gabriel, Reina, Miguel, Hernandez-Ayala, Luis Felipe, Galano, Annia
Publicada:
1 jun 2023
Resumen:
Ferulic acid has numerous beneficial effects on human health, which are
frequently attributed to its antioxidant behavior. In this report, many
of them are reviewed, and 185 new ferulic acid derivatives are
computationally designed using the CADMA-Chem protocol. Consequently,
their chemical space was sampled and evaluated. To that purpose,
selection and elimination scores were used, which are built from a set
of descriptors accounting for ADME properties, toxicity, and synthetic
accessibility. After the first screening, 12 derivatives were selected
and further investigated. Their potential role as antioxidants was
predicted from reactivity indexes directly related to the formal
hydrogen atom transfer and the single electron transfer mechanisms. The
best performing molecules were identified by comparisons with the parent
molecule and two references: Trolox and & alpha;-tocopherol. Their
potential as polygenic neuroprotectors was investigated through the
interactions with enzymes directly related to the etiologies of
Parkinson's and Alzheimer's diseases. These enzymes are
acetylcholinesterase, catechol-O-methyltransferase, and monoamine
oxidase B. Based on the obtained results, the most promising candidates
(FA-26, FA-118, and FA-138) are proposed as multifunctional antioxidants
with potential neuroprotective effects. The findings derived from this
investigation are encouraging and might promote further investigations
on these molecules.
Filiaciones:
Guzman-Lopez, Eduardo Gabriel:
Univ Autonoma Metropolitana Iztapalapa, Dept Quim, Ave Ferrocarril San Rafael Atlixco 186,Col Leyes d, Mexico City 09310, Mexico
Reina, Miguel:
Univ Nacl Autonoma Mexico, Fac Quim, Dept Quim Inorgan & Nucl, Mexico City 04510, Mexico
Hernandez-Ayala, Luis Felipe:
Univ Autonoma Metropolitana Iztapalapa, Dept Quim, Ave Ferrocarril San Rafael Atlixco 186,Col Leyes d, Mexico City 09310, Mexico
Galano, Annia:
Univ Autonoma Metropolitana Iztapalapa, Dept Quim, Ave Ferrocarril San Rafael Atlixco 186,Col Leyes d, Mexico City 09310, Mexico
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