Synthesis and pharmacological properties of novel guanidine derivatives of quinazoline-2,4(1H,3H)-dione

Synthesis and pharmacological properties of novel guanidine derivatives of quinazoline-2,4(1H,3H)-dione

Introduction: Na+/H+ exchanger type 1 (NHE-1) is a validated drug target for the treatment of cardiovascular and ophthalmic diseases due to the cytoprotective, anti-ischemic and anti-inflammatory properties of NHE-1 inhibitors. This article presents data on the synthesis and pharmacological activity...

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Published in:Research results in pharmacology (English ed.) Vol. 10; no. 3; pp. 73 - 84
Main Authors: Ozerov, Alexander A., Merezhkina, Daria V., Gurova, Natalia A., Naumenko, Lyudmila V., Babkov, Denis A., Sirotenko, Victor S., Litvinov, Roman A., Taran, Alena S., Stepanova, Nadezhda V., Ibragimova, Umida M., Spasov, Alexander A., Kosolapov, Vadim A.
Format: Journal Article
Language:English
Published: 23-09-2024
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Summary:Introduction: Na+/H+ exchanger type 1 (NHE-1) is a validated drug target for the treatment of cardiovascular and ophthalmic diseases due to the cytoprotective, anti-ischemic and anti-inflammatory properties of NHE-1 inhibitors. This article presents data on the synthesis and pharmacological activity studies of novel guanidine derivatives of quinazoline-2,4(1H,3H)-dione 6-11 and reference drugs amiloride, rimeporide, zoniporide, dexamethasone, aminoguanidine, and acetylsalicylic acid. Materials and Methods: Pharmacological properties were assessed using pH-dependent platelets deformation assay, anti-inflammatory activity assay on LPS-stimulated peritoneal macrophages, antiglycation assay, analysis of platelet aggregation in vitro and measurement of intraocular pressure in vivo. Results: Several compounds combine NHE-1 inhibition with antiglaucomic and antiplatelet activity. Compound 11 significantly inhibits pro-inflammatory activation of murine macrophages (IC50 15.64 μM) and effectively suppresses the formation of glycated proteins (38.1±2.6% in C 1 mM). Conclusion: The investigated compounds represent a promising scaffold for development of agents for the treatment of cardiovascular pathologies, glaucoma, excessive inflammation, and late diabetic complications including retina diabetics and thrombosis.
ISSN:2658-381X
2658-381X
DOI:10.18413/rrpharmacology.10.486