Effect of Guanidine Derivatives of Quinazoline on Na + /H + -Exchanger and Intraocular Pressure

A. S. Taran; Таран А. С.; L. V. Naumenko; Науменко Л. В.; Ju. A. Govorova; Говорова Ю. А.; N. A. Gurova; Гурова Н. А.; A. A. Spasov; Спасов А. А.; A. A. Ozerov; Озеров А. А.; D. V. Merezhkina; Мережкина Д. В.

doi:10.31857/S0132342323020215

Effect of Guanidine Derivatives of Quinazoline on Na⁺/H⁺-Exchanger and Intraocular Pressure

Авторлар: Taran A.S.¹^,2, Naumenko L.V.¹, Govorova J.A.¹, Gurova N.A.¹, Spasov A.A.¹^,2, Ozerov A.A.¹^,2, Merezhkina D.V.¹
Мекемелер:
1. Volgograd State Medical University, Ministry of Healthcare of the Russian Federation
2. Volgograd Medical Scientific Center
Шығарылым: Том 49, № 2 (2023)
Беттер: 207-215
Бөлім: Articles
URL: https://journal-vniispk.ru/0132-3423/article/view/145879
DOI: https://doi.org/10.31857/S0132342323020215
EDN: https://elibrary.ru/PGNDUV
ID: 145879

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Аннотация

Based on the data of the role of Na⁺/H⁺-exchanger (NHE) in the modulation of intraocular pressure, which is the main factor in the development of glaucoma, and previously conducted studies by various authors proving the presence of inhibitory NHE-1 activity in quinazoline derivatives, nine new compounds belonging to this class were synthesized. The effect of the obtained quinazoline derivatives on the inhibition of Na⁺/H⁺-exchanger and their on intraocular pressure (IOP) in comparison with zoniporide (NHE inhibitor) and timolol (a drug for lowering IOP used in clinical practice) was studied. Among the compounds studied in vitro, all quinazoline derivatives at a concentration of 1 nM inhibited the activity of NHE-1, the most active compound was a derivative of quinazoline acetylguanidine. However, not all compounds showed IOP-reducing activity in vivo in rats. So the most active of the quinazoline derivatives are 4-oxoquinazoline acetylguanidine, its brominated derivative at position C6 and quinazoline propionylguanidine. The structure–activity analysis showed that the presence of the Br atom at the C6 position of the 4-oxoquinazoline acetylguanidine derivative leads to a maximum decrease in IOP during instillation of the solution of the compound.

Негізгі сөздер

Na⁺/H⁺-exchanger (NHE), intraocular pressure (IOP), glaucoma, quinazoline, melatonin bioisosters

Әдебиет тізімі

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