Guanidine Derivatives of Quinazoline-2,4(1H,3H)-Dione as NHE-1 Inhibitors and Anti-Inflammatory Agents.
Life (Basel)
; 12(10)2022 Oct 20.
Article
en En
| MEDLINE
| ID: mdl-36295082
ABSTRACT
Quinazolines are a rich source of bioactive compounds. Previously, we showed NHE-1 inhibitory, anti-inflammatory, antiplatelet, intraocular pressure lowering, and antiglycating activity for a series of quinazoline-2,4(1H,3H)-diones and quinazoline-4(3H)-one guanidine derivatives. In the present work, novel N1,N3-bis-substituted quinazoline-2,4(1H,3H)-dione derivatives bearing two guanidine moieties were synthesized and pharmacologically profiled. The most potent NHE-1 inhibitor 3a also possesses antiplatelet and intraocular-pressure-reducing activity. Compound 4a inhibits NO synthesis and IL-6 secretion in murine macrophages without immunotoxicity and alleviates neutrophil infiltration, edema, and tissue lesions in a model of LPS-induced acute lung injury. Hence, we considered quinazoline derivative 4a as a potential agent for suppression of cytokine-mediated inflammatory response and acute lung injury.
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1
Colección:
01-internacional
Base de datos:
MEDLINE
Idioma:
En
Revista:
Life (Basel)
Año:
2022
Tipo del documento:
Article
País de afiliación:
Rusia