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Название: | Prospects for the use of sulfur-containing pteridines in toxic liver damage |
Авторы: | Lohvinenko, N. Shvets, V. M. Berest, G. H. Nosulenko, I. S. Voskoboinik, O. Severina, H. Okovytyy, S. Kovalenko, S. Швець, Володимир Миколайович Берест, Галина Григорівна Носуленко, Інна Степанівна |
Ключевые слова: | pteridines inhibition of linoleic acid peroxidation determination of glutathione in liver homogenate hepatoprotective activity free-radical scavenging activity tetrachloromethane hepatitis in rats |
Дата публикации: | 2024 |
Библиографическое описание: | Prospects for the use of sulfur-containing pteridines in toxic liver damage / N. Lohvinenko, V. Shvets, G. Berest, I. Nosulenko, O. Voskoboinik, H. Severina, S. Okovytyy, S. Kovalenko // Regulatory Mechanisms in Biosystems. - 2024. - Vol. 15, N 2. - P. 374-381. - https://doi.org/10.15421/022453. |
Аннотация: | The presented material describes the results of the purposeful search for the novel hepatoprotective agents among
synthetic sulfur-containing pteridines. The studied compounds were obtained using previously described synthetic procedures.
SwissADME and ProTox-II services, as well as a docking study were used to predict the compounds` pharmacokinetics,
drug-likeness and toxicity. The effects of sulfur-containing pteridines on lipid peroxidation in vitro and
GSH/GSSG levels in vivo were studied for evaluation of their hepatoprotective potential. In silico procedures allowed us
to exclude the compounds with inappropriate ADME parameters and high predicted toxicity. Molecular docking of the
obtained compounds towards the active site of CYP-enzyme allowed us to clarify the specifics of ligand-enzyme interactions
and predict cytochrome-inhibiting activity of the studied agents. The antioxidant activity of the studied compounds
was evaluated in vitro using the linoleic acid peroxidation model. It has been found that sulfur-containing pteridines
inhibit the peroxidation of linoleic acid. The structure – antioxidant activity relationships were evaluated and discussed as
well. Additionally, it has been estimated that antioxidant properties of the studied pteridines directly correlate with their
hydrophilicity and number of functional groups with exchangeable proton in molecules. In vivo studies showed that
some of the studied sulfur-containing pteridines reduced severity of the hepatotoxic effects caused by the administration
of carbon tetrachloride. (3-(7-Hydroxy-4-oxo-2-thioxo-1,2,3,4-tetrahydropteridin-6-yl)propanoyl)alanine has been identified
as the most active hepatoprotective agent. The above mentioned compound significantly increases the content of
GSH and decreases the level of GSSG compared with non-treated experimental pathology, which reliably affirms its
hepatoprotective activity. The hepatoprotective activity of the studied compounds is likely associated with their ability to
increase the level of GSH, inhibit lipid peroxidation and decrease prooxidant compounds levels. The obtained results
attest the reasonability of further search for hepatoprotective agents among sulfur-containing pteridine derivatives. |
URI: | http://dspace.zsmu.edu.ua/handle/123456789/21189 |
Располагается в коллекциях: | Наукові праці. (Фармакогнозія) Наукові праці. (Клінічна фармація ННІПО) Наукові праці. (Біохімія)
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