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In vitro antioxidant activities of five β-carboline alkaloids, molecular docking, and dynamic simulations

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Abstract

Experimental and computational studies were performed to determine the antioxidant activities of harmine, harmaline, harmalol, harmane, and 1,2,3,4-tetrahydroharmane-3-carboxylic acid. The in vitro study was conducted using H2O2, ABTS, FRAP and PR tests. The theoretical study was performed using density functional theory (DFT), molecular docking, and molecular dynamics. The in vitro study showed high hydrogen peroxide scavenging activity 27.63 ± 1.74% for harmine which is significantly greater than ascorbic acid (8.02 ± 0.58%). Harmalol has shown the highest antioxidant activity for ABTS, FRAP, and reducing power with 371.15 ± 1.80 µg TE/mg, 11.30 ± 0.01 µg TE/mg, and 671.70 ± 5.11 µg AAE/mg, respectively. DFT analysis indicates that harmalol and harmaline are the most reactive molecules and could scavenge free radicals through the SET-PT mechanism. The docking analysis revealed that harmalol and harmaline have low binding energy and interact through hydrogen and van der Waals bonds with the myeloperoxidase receptor. In addition, molecular dynamics revealed that the protein–ligand equilibrium is stable after 100,000 fs, indicating that harmaline and harmalol could be inhibitors of myeloperoxidase. The obtained results were used to design new harmalol derivative, with promising in silico results. The results of this work showed that harmalol and harmaline have high antioxidant activity in vitro and in silico.

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Abbreviations

H2O2 :

Hydrogen peroxide scavenging

ABTS:

Radical Trolox equivalent antioxidant capacity cation-decolorization

FRAP:

Ferric reducing-antioxidant power

RP:

Reducing power

ADME/Tox:

Absorption, distribution, metabolism, excretion, and toxicity

B3LYP:

Becke 3-Parameter, Lee, Yang and Parr

BDE (N–H):

N–H bond dissociation enthalpy

DFT:

Density functional theory

EA:

Electron affinity

EHOMO:

Highest occupied molecular orbital energy

ELUMO:

Lowest unoccupied molecular orbital energy

ETE:

Electron transfer enthalpy

IP:

Ionization potential

MD:

Molecular dynamics

MMFF94:

Merck molecular force field

MPO:

Myeloperoxidase

PA:

Proton affinity

PDE:

Proton dissociation enthalpy

RMSD:

Root mean standard deviation

S:

Softness

THCA:

1,2,3,4-Tetrahydroharmane-3-carboxylic acid

ƞ:

Hardness

µ:

Chemical potential

χ:

Electronegativity

ω:

Electrophilic index

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Acknowledgements

The authors wish to thank the Sidi Mohamed Ben Abdellah University (USMBA) of Fez, Morocco.

Funding

This study was supported by the Sidi Mohamed Ben Abdellah University (USMBA) of Fez, Morocco.

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Authors and Affiliations

  1. Laboratory of Natural Substances, Pharmacology, Environment, Modeling, Health & Quality of Life (SNAMOPEQ), Polydisciplinary Faculty of Taza, Sidi Mohamed Ben Abdellah University (USMBA), B.P.: 1223, Taza-Gare, Taza, Morocco

    Souad Senhaji, Fatima Lamchouri, Taoufik Akabli & Hamid Toufik

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  1. Souad Senhaji
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  2. Fatima Lamchouri
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SS performed experimental studies, statistical analysis, and manuscript preparation. FL designed the experiments and consistent guidance; analyzed the data, manuscript preparation, and review; edited the final version; and submitted it for publication. TA in silico studies and manuscript preparation. HT designed the experiments and provided consistent guidance and manuscript preparation and review.

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Correspondence to Fatima Lamchouri.

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Senhaji, S., Lamchouri, F., Akabli, T. et al. In vitro antioxidant activities of five β-carboline alkaloids, molecular docking, and dynamic simulations. Struct Chem 33, 883–895 (2022). https://doi.org/10.1007/s11224-022-01886-3

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