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. 2023 Apr 28;24(9):8046.
doi: 10.3390/ijms24098046.

Study of the Magnesium Comenate Structure, Its Neuroprotective and Stress-Protective Activity

Stanislav Kozin  1   2   3 , Alexandr Kravtsov  1   2   3 , Lev Ivashchenko  3   4 , Victor Dotsenko  4 , Lada Vasilyeva  4 , Alexander Vasilyev  4 , Elena Tekutskaya  1 , Nicolai Aksenov  5 , Mikhail Baryshev  1   2 , Anna Dorohova  1   2 , Lilia Fedulova  6 , Stepan Dzhimak  1   2
Affiliations

Study of the Magnesium Comenate Structure, Its Neuroprotective and Stress-Protective Activity

Stanislav Kozin et al. Int J Mol Sci. .

Abstract

The crystal structure and the biological activity of a new coordination compound of magnesium ions with comenic acid, magnesium comenate, was characterized and studied. Quantitative and qualitative analysis of the compound was investigated in detail using elemental X-ray fluorescent analysis, thermal analysis, IR-Fourier spectrometry, UV spectroscopy, NMR spectroscopy, and X-ray diffraction analysis. Based on experimental analytical data, the empirical formula of magnesium comenate [Mg(HCom)2(H2O)6]·2H2O was established. This complex compound crystallizes with eight water molecules, six of which are the hydration shell of the Mg2+ cation, and two more molecules bind the [Mg(H2O)6]2+ aquacation with ionized ligand molecules by intermolecular hydrogen bonds. The packing of molecules in the crystal lattice is stabilized by a branched system of hydrogen bonds with the participation of solvate water molecules and oxygen atoms of various functional groups of ionized ligand molecules. With regard to the biological activity of magnesium comenate, a neuroprotective, stress-protective, and antioxidant effect was established in in vitro and in vivo models. In in vitro experiments, magnesium comenate protected cerebellar neurons from the toxic effects of glutamate and contributed to the preservation of neurite growth parameters under oxidative stress caused by hydrogen peroxide. In animal studies, magnesium comenate had a stress-protective and antioxidant effect in models of immobilization-cold stress. Oral administration of magnesium comenate at a dose of 2 mg/kg of animal body weight for 3 days before stress exposure and for 3 days during the stress period led to a decrease in oxidative damage and normalization of the antioxidant system of brain tissues against the background of induced stress. The obtained results indicate the advisability of further studies of magnesium comenate as a compound potentially applicable in medicine for the pharmacological correction of conditions associated with oxidative and excitotoxic damage to nerve cells.

Keywords: antioxidants; comenic acid; excitotoxicity; immobilization stress; magnesium complex compounds; magnesium ions; neuritic growth; neuroprotectors.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Infrared spectra: (a) comenic acid; (b) complex compound [Mg(Hcom)2(H2O)6]·2H2O.
Figure 1
Figure 1
Infrared spectra: (a) comenic acid; (b) complex compound [Mg(Hcom)2(H2O)6]·2H2O.
Figure 2
Figure 2
TG, DTG, DSC curves of a complex compound [Mg(Hcom)2(H2O)6]·2H2O.
Figure 3
Figure 3
General view of a molecule of magnesium complex compound with 5-hydroxy-4-oxo-4H-pyran-2-carboxylic acid in a crystal.
Figure 4
Figure 4
Short intermolecular contacts.
Figure 5
Figure 5
Effect of magnesium comenate on the growth of neurites in the spinal ganglia of chickens under normal conditions (a) and oxidative stress (b) (OS). *—p < 0.05 in relation to control, +—p < 0.05 in relation to oxidative stress.
Figure 6
Figure 6
Effect of magnesium comenate, comenic acid (CA) and magnesium sulfate (MS) on the survival of cultured rat cerebellar neurons: (a) under normal conditions and (b) under excitotoxic effects of glutamate (Glu). *—p < 0.05 in relation to the control, +—p < 0.05 in relation to the point “Glu + MC 0.1 mM”.
Figure 7
Figure 7
Effect of magnesium comenate on the MDA level and chemiluminescence intensity (ChI) in the brain tissues of rats under stress. *—p < 0.05 in relation to control, +—p < 0.05 in relation to stress.
Figure 8
Figure 8
Effect of magnesium comenate on the activity of SOD and catalase in the brain tissues of rats under stress. *—p < 0.05 in relation to control, +—p < 0.05 in relation to stress.
Figure 9
Figure 9
Effect of magnesium comenate on the content of reduced glutathione (GSH), activity of glutathione peroxidase (GPO), and glutathione reductase (GR) in rat brain tissues under stress. *—p < 0.05 in relation to control, +—p < 0.05 in relation to stress.
Scheme 1
Scheme 1
Synthesis of magnesium comenate.
See this image and copyright information in PMC

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