19-Hydroxyeicosatetraenoic acid analogs: Antagonism of 20-hydroxyeicosatetraenoic acid-induced vascular sensitization and hypertension

Autor: Fan Zhang, Michal L. Schwartzman, Rambabu Dakarapu, Vijaya L. Manthati, Victor Garcia, Adeniyi Michael Adebesin, D. K. Barma, John R. Falck, Deepan Barma, Ramu Errabelli
Rok vydání: 2019
Předmět:
Male
Clinical Biochemistry
Kidney Glomerulus
Pharmaceutical Science
Pharmacology
01 natural sciences
Biochemistry
Article
chemistry.chemical_compound
Mice
Phenylephrine
In vivo
Drug Discovery
Hydroxyeicosatetraenoic Acids
medicine
Animals
Vasoconstrictor Agents
Cytochrome P450 Family 4
Molecular Biology
Sensitization
Antihypertensive Agents
Mice
Knockout
biology
010405 organic chemistry
Organic Chemistry
Hydroxyeicosatetraenoic acid
Cytochrome P450
hemic and immune systems
20-Hydroxyeicosatetraenoic acid
0104 chemical sciences
010404 medicinal & biomolecular chemistry
medicine.anatomical_structure
chemistry
Eicosanoid
Hypertension
Microvessels
biology.protein
cardiovascular system
Molecular Medicine
lipids (amino acids
peptides
and proteins)
Antagonism
medicine.drug
circulatory and respiratory physiology
Zdroj: Bioorg Med Chem Lett
ISSN: 1464-3405
Popis: 19-Hydroxyeicosatetraenoic acid (19-HETE, 1), a metabolically and chemically labile cytochrome P450 eicosanoid, has diverse biological activities including antagonism of the vasoconstrictor 20-hydroxyeicosatetraenoic acid (20-HETE, 2). A SAR study was conducted to develop robust analogs of 1 with improved in vitro and in vivo efficacy. Analogs were screened in vitro for inhibition of 20-HETE-induced sensitization of rat renal preglomerular microvessels toward phenylephrine and demonstrated to normalize the blood pressure of male Cyp4a14(-/-) mice that display androgen-driven, 20-HETE-dependent hypertension.
Databáze: OpenAIRE
Externí odkaz: