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, J R Falck

Research output: Contribution to journalArticle

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

Fingerprint

Hydroxyeicosatetraenoic Acids
Blood Vessels
Hypertension
Eicosanoids
Blood pressure
Phenylephrine
Vasoconstrictor Agents
Microvessels
Bioactivity
Cytochrome P-450 Enzyme System
Androgens
Rats
Blood Pressure
Kidney
20-hydroxy-5,8,11,14-eicosatetraenoic acid
In Vitro Techniques

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

Cite this

19-Hydroxyeicosatetraenoic acid analogs : Antagonism of 20-hydroxyeicosatetraenoic acid-induced vascular sensitization and hypertension. / Dakarapu, Rambabu; Errabelli, Ramu; Manthati, Vijaya L.; Michael Adebesin, Adeniyi; Barma, Deb K.; Barma, Deepan; Garcia, Victor; Zhang, Fan; Laniado Schwartzman, Michal; Falck, J R.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 29, No. 19, 126616, 01.10.2019.

Research output: Contribution to journalArticle

Dakarapu, R, Errabelli, R, Manthati, VL, Michael Adebesin, A, Barma, DK, Barma, D, Garcia, V, Zhang, F, Laniado Schwartzman, M & Falck, JR 2019, '19-Hydroxyeicosatetraenoic acid analogs: Antagonism of 20-hydroxyeicosatetraenoic acid-induced vascular sensitization and hypertension', Bioorganic and Medicinal Chemistry Letters, vol. 29, no. 19, 126616. https://doi.org/10.1016/j.bmcl.2019.08.020
Dakarapu, Rambabu ; Errabelli, Ramu ; Manthati, Vijaya L. ; Michael Adebesin, Adeniyi ; Barma, Deb K. ; Barma, Deepan ; Garcia, Victor ; Zhang, Fan ; Laniado Schwartzman, Michal ; Falck, J R. / 19-Hydroxyeicosatetraenoic acid analogs : Antagonism of 20-hydroxyeicosatetraenoic acid-induced vascular sensitization and hypertension. In: Bioorganic and Medicinal Chemistry Letters. 2019 ; Vol. 29, No. 19.
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