CADMA-Chem: A Computational Protocol Based on Chemical Properties Aimed to Design Multifunctional Antioxidants

Guzmán‐López, Eduardo Gabriel; Reina, Miguel; Pérez-González, Adriana; Francisco‐Márquez, Misaela; Hernández‐Ayala, Luis Felipe; Castañeda‐Arriaga, Romina; Galano, Annia

doi:10.3390/ijms232113246

Cited by 10 publications

(15 citation statements)

References 173 publications

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“…Accordingly, for the thermochemical and kinetic studies in the aqueous solution, only neutral and acid-base species with f ≥ 0.01 (more than 1%) are considered. This is because the multifunctional antioxidants are expected to enter the cells by passively crossing biological membranes [ 43 ]. On the contrary, in lipid-like media, which does not promote the necessary solvation to stabilize the ionic species, the neutral forms are prevalent.…”

Section: Resultsmentioning

confidence: 99%

In Silico and In Vitro Study of Antioxidant Potential of Urolithins

et al. 2023

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In this work, quantum chemical calculations based on density functional theory (DFT) were performed to predict the antioxidant potential of four bioactive gut microbiota metabolites of the natural polyphenols ellagitannins (ETs) and ellagic acid (EA), also known as urolithins (UROs). In order to evaluate their ability to counter the effect of oxidative stress caused by reactive oxygen species (ROS), such as the hydroperoxyl radical (•OOH), different reaction mechanisms were investigated, considering water and lipid-like environments. Through our in silico results, it emerged that at physiological pH, the scavenging activity of all urolithins, except urolithin B, are higher than that of trolox and other potent antioxidants existing in nature, such as EA, α-mangostin, allicin, caffeine and melatonin. These findings were confirmed by experimental assays.

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Section: Resultsmentioning

confidence: 99%

In Silico and In Vitro Study of Antioxidant Potential of Urolithins

et al. 2023

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“…The reparative capabilities of the substance on a range of vital biomolecules were assessed using a recently proposed computational procedure. 52 This involved studies on a simplified linoleic acid model that represents unsaturated fatty acids, six N -formyl derivatives of amino acids that are highly vulnerable to oxidative damage, such as Cys, Leu, Tyr, Trp, Met, and His, and DNA fragments of 2′-deoxyguanosine, which are the nucleosides most easily oxidized. Antioxidants are able to use either the SET or f -HAT mechanisms, or a combination of both, to restore and regenerate these biomolecules.…”

Section: Methodsmentioning

confidence: 99%

Theoretical Insights into the Oxidative Stress-Relieving Properties of Pinocembrin─An Isolated Flavonoid from Honey and Propolis

Spiegel

2023

J. Phys. Chem. B

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Bee products are a valuable group of substances that have a wide range of applications for humans. They contain a high level of polyphenolic compounds, which have been shown to combat radicals and effectively reduce oxidative stress. In this study, density functional theory was utilized to determine the anti-OOH activity, sequestration of free Cu(II) and Fe(III) ions, the potential pro-oxidative activity of the formed complexes, and the repairing capabilities toward essential biomolecules. The kinetic constants for scavenging of hydroperoxide radical were found to be low, with an order of magnitude not exceeding 10 −3 M −1 s −1 . Chelating properties showed slightly more satisfactory outcomes, although most complexes exhibited pro-oxidant activity. Pinocembrin, however, proved effective in repairing oxidatively damaged biological compounds and restoring their original functionality. The study found that whilst the system displays limited type I and type II antioxidant activity, it may support the role of physiological reductants already present in the biological matrix.

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“…S P is a measure of the tested compounds' capacity to bind to the enzymes compared with natural substrates (COMT: dopamine (dopa), MAO-B phenylethylamine (pea) and AChE: acetylcholine (ACh). It was defined according to our previous reports [136,137] as:…”

Section: Polygenic Activitymentioning

confidence: 99%

Rational Design of Multifunctional Ferulic Acid Derivatives Aimed for Alzheimer’s and Parkinson’s diseases

Guzmán‐López¹,

Reina²,

Hernández‐Ayala³

et al. 2023

Preprint

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Ferulic acid has numerous beneficial effects for 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. For the later, the 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, directed related with 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 directed related with the etiologies of Parkinson’s and Alzheimer’s diseases. They 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.

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CADMA-Chem: A Computational Protocol Based on Chemical Properties Aimed to Design Multifunctional Antioxidants

Cited by 10 publications

References 173 publications

In Silico and In Vitro Study of Antioxidant Potential of Urolithins

In Silico and In Vitro Study of Antioxidant Potential of Urolithins

Theoretical Insights into the Oxidative Stress-Relieving Properties of Pinocembrin─An Isolated Flavonoid from Honey and Propolis

Rational Design of Multifunctional Ferulic Acid Derivatives Aimed for Alzheimer’s and Parkinson’s diseases

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