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

Rambabu Dakarapu, Ramu Errabelli, Vijaya L. Manthati, Adeniyi Michael Adebesin, Deb K. Barma, Deepan Barma, Victor Garcia, Fan Zhang, Michal Laniado Schwartzman, John R. Falck

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number126616
JournalBioorganic and Medicinal Chemistry Letters
Volume29
Issue number19
DOIs
StatePublished - Oct 1 2019

Keywords

  • Antagonist
  • Bioisosteric replacement
  • Eicosanoid
  • Hypertension
  • QDEGARKRKXEQDF-AAHZGTINSA-M
  • Vascular sensitization

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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