Chemoreactome analysis of methylethylpyridinol and possible mechanisms of ophthalmoprotection

Introduction. Methylethylpyridinol (MEPD or Emoxypine) is widely used in practice to treat various eye diseases, exhibiting angioprotective, antiplatelet, antioxidant effects. The molecular mechanisms for the implementation of these and other pharmacological effects of MEPD are not entirely obvious.

Aim. To conduct a chemoreactome analysis of MEPD aimed at identifying the molecular mechanisms of the drug action. Materials and methods. The pharmacological/biological properties of MEPD were assessed using methods for chemoinformatic analysis of molecules developed in the scientific school of RAS academicians Yu.I. Zhuravlev and K.V. The analysis procedure is based on the latest machine learning technologies developed in the theory of topological and metric analysis of feature descriptions in application to chemographs.

Results and discussion. The results of chemoproteomic profiling of MEPD showed anti-inflammatory, antihypoxic, antioxidant, vasoprotective and vasorelaxant effects of the drug. By inhibiting arachidonate-5-lipoxygenase, leukotriene A4 hydrolase, leu kotriene LTB4 and prostanoid receptors, inhibiting the production of superoxide anions and leukotriene, MEPD helps to reduce local inflammation in eye tissues. Evaluations of the vasodynamic and neuroprotective effects of MEPD in vitro, obtained as a result of chemoreactome analysis, indicated neurotrophic, neuroprotective and vasodilatory effects of MEPD. The neurotrophic effect in vitro in cultured sensory neurons and neuroprotective activity, assessed by the protective effect against L-homocysteine, exceeded the activity of control molecules. The analysis demonstrated the vasodilatory activity of MEPD and the reduction of intraocular pressure in vivo.

Conclusions. Based on the results of the chemoreactome analysis, new molecular mechanisms of the anti-inflammatory action of MEPD in eye tissues were proposed, carried out through the inhibition of certain target proteins. The antioxidant properties of MEPD can be associated with both specific interactions with proteome proteins (e.g., activation of antioxidant proteins) and with the direct action of the molecule on reactive oxygen species.

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