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

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.

Structure and Neuroprotector Properties of a Complex Compound of Lithium with Comenic Acid

“…The presence of a hydroxyl residue in the third position and the pyran ring makes it possible for the comenic acid residue to neutralize free radicals and suppress the development of oxidative stress, reducing the toxic effect of glutamate. It should be noted that the protective effect of comenic acid during excitotoxic exposure, which we studied earlier [7], was significantly lower than that of lithium comenate and is about 20% at a concentration of 1 mM and about 10% at a concentration of 0.1-0.01 mM. At the same time, lithium chloride in our experiments did not have a neuroprotective effect.…”

“…The protective effect of lithium comenate on the culture of cerebellar neurons in our study can be explained by the biological effects of lithium and comenic acid residue (comenate). In one of our past works [ 7 ], we showed that comenic acid has the effect of a direct antioxidant, participating in the inhibition of free radical oxidation processes in model systems. The presence of a hydroxyl residue in the third position and the pyran ring makes it possible for the comenic acid residue to neutralize free radicals and suppress the development of oxidative stress, reducing the toxic effect of glutamate.…”

“…Comenic acid is a representative of 4H-pyrones (or γ-pyrones). Regarding this class of compounds ( Figure 1 ), there are data in the literature indicating a high therapeutic potential in preclinical studies [ 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 ].…”

“…This effect is expressed as a decrease in the level of neuron death and a decrease in the number of calcium ions in the cytosol [ 18 ]. In addition to these properties, it has a neurotrophic effect; prevents the disruption of synaptic plasticity of hippocampal neurons under stress; and has antioxidant, moderately anti-amnestic and anxiolytic effects [ 7 , 19 , 20 , 21 ].…”

“…Comenic acid is a representative of 4H-pyrones (or γ-pyrones). Regarding this class of compounds (Figure 1), there are data in the literature indicating a high therapeutic potential in preclinical studies [6][7][8][9][10][11][12][13][14][15]. It should be noted that comenic acid is an active component of the drug baliz-2, used for cell regeneration in various pathologies [16,17].…”