Effect of Guanidine Derivatives of Quinazoline on the Na+/H+ Exchanger and Intraocular Pressure in Rats

• Published in: Russian journal of bioorganic chemistry 2023-04, Vol.49 (2), p.352-359
• Main Authors: Taran, A. S., Naumenko, L. V., Govorova, Yu. A., Gurova, N. A., Spasov, A. A., Ozerov, A. A., Merezhkina, D. V.
• Format: Article
• Language: English
• Subjects: Biochemistry; Biomedical and Life Sciences; Biomedicine; Bioorganic Chemistry; Bromination; Glaucoma; Intraocular pressure; Life Sciences; Organic Chemistry
• ISSN: 1068-1620; 1608-330X
• DOI: 10.1134/S1068162023020218

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