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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| Format: | Article |
| Language: | English |
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Belgorod National Research University
2024-09-01
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| Series: | Research Results in Pharmacology |
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| Online Access: | https://rrpharmacology.ru/index.php/journal/article/view/486 |
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| author | Alexander A. Ozerov Daria V. Merezhkina Natalia A. Gurova Lyudmila V. Naumenko Denis A. Babkov Victor S. Sirotenko Roman A. Litvinov Alena S. Taran Nadezhda V. Stepanova Umida M. Ibragimova Alexander A. Spasov Vadim A. Kosolapov |
| author_facet | Alexander A. Ozerov Daria V. Merezhkina Natalia A. Gurova Lyudmila V. Naumenko Denis A. Babkov Victor S. Sirotenko Roman A. Litvinov Alena S. Taran Nadezhda V. Stepanova Umida M. Ibragimova Alexander A. Spasov Vadim A. Kosolapov |
| author_sort | Alexander A. Ozerov |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-3a04ee4298fc43a9a23160b590cbcd08 |
| institution | Kabale University |
| issn | 2658-381X |
| language | English |
| publishDate | 2024-09-01 |
| publisher | Belgorod National Research University |
| record_format | Article |
| series | Research Results in Pharmacology |
| spelling | doaj-art-3a04ee4298fc43a9a23160b590cbcd082025-01-08T12:36:33ZengBelgorod National Research UniversityResearch Results in Pharmacology2658-381X2024-09-01103738410.18413/rrpharmacology.10.486Synthesis and pharmacological properties of novel guanidine derivatives of quinazoline-2,4(1H,3H)-dioneAlexander A. Ozerov0https://orcid.org/0000-0002-4721-0959Daria V. Merezhkina1https://orcid.org/0000-0002-9848-7149Natalia A. Gurova2https://orcid.org/0000-0002-0670-1444Lyudmila V. Naumenko3https://orcid.org/0000-0002-2119-4233Denis A. Babkov4https://orcid.org/0000-0002-9645-3324Victor S. Sirotenko5https://orcid.org/0000-0003-2249-020XRoman A. Litvinov6https://orcid.org/0000-0002-0162-0653Alena S. Taran7https://orcid.org/0000-0001-8477-254XNadezhda V. Stepanova8https://orcid.org/0000-0002-6629-3729Umida M. Ibragimova9https://orcid.org/0000-0001-9141-4417Alexander A. Spasov10https://orcid.org/0000-0002-7185-4826Vadim A. Kosolapov11https://orcid.org/0000-0002-6702-1207Volgograd State Medical UniversityVolgograd State Medical UniversityVolgograd State Medical UniversityVolgograd State Medical UniversityVolgograd State Medical UniversityVolgograd State Medical UniversityVolgograd State Medical UniversityVolgograd State Medical UniversityVolgograd State Medical UniversityVolgograd State Medical UniversityVolgograd State Medical UniversityVolgograd State Medical UniversityIntroduction: 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.https://rrpharmacology.ru/index.php/journal/article/view/486na /h -exchangernhe-1guanidine derivatives of quinazolineantiglaucomic actionantiglycationantiplatelet activity |
| spellingShingle | Alexander A. Ozerov Daria V. Merezhkina Natalia A. Gurova Lyudmila V. Naumenko Denis A. Babkov Victor S. Sirotenko Roman A. Litvinov Alena S. Taran Nadezhda V. Stepanova Umida M. Ibragimova Alexander A. Spasov Vadim A. Kosolapov Synthesis and pharmacological properties of novel guanidine derivatives of quinazoline-2,4(1H,3H)-dione Research Results in Pharmacology na /h -exchanger nhe-1 guanidine derivatives of quinazoline antiglaucomic action antiglycation antiplatelet activity |
| title | Synthesis and pharmacological properties of novel guanidine derivatives of quinazoline-2,4(1H,3H)-dione |
| title_full | Synthesis and pharmacological properties of novel guanidine derivatives of quinazoline-2,4(1H,3H)-dione |
| title_fullStr | Synthesis and pharmacological properties of novel guanidine derivatives of quinazoline-2,4(1H,3H)-dione |
| title_full_unstemmed | Synthesis and pharmacological properties of novel guanidine derivatives of quinazoline-2,4(1H,3H)-dione |
| title_short | Synthesis and pharmacological properties of novel guanidine derivatives of quinazoline-2,4(1H,3H)-dione |
| title_sort | synthesis and pharmacological properties of novel guanidine derivatives of quinazoline 2 4 1h 3h dione |
| topic | na /h -exchanger nhe-1 guanidine derivatives of quinazoline antiglaucomic action antiglycation antiplatelet activity |
| url | https://rrpharmacology.ru/index.php/journal/article/view/486 |
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