19-Hydroxyeicosatetraenoic Acid Analogs: Antagonism of 20-Hydroxyeicosatetraenoic Acid-Induced Vascular Sensitization and Hypertension

Authors

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

DOI

10.1016/j.bmcl.2019.08.020

Journal Title

Bioorganic & Medicinal Chemistry Letters

First Page

126616

Document Type

Article

Publication Date

October 2019

Department

Pharmacology

Keywords

Antagonist, Bioisosteric replacement, Eicosanoid, Hypertension, Vascular sensitization

Disciplines

Medicine and Health Sciences

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.

Recommended Citation

Dakarapu, R., Errabelli, R., Manthati, V., Michael Adebesin, A., Barma, D., Barma, D., Garcia, V., Zhang, F., Laniado Schwartzman, M., & Falck, J. (2019). 19-Hydroxyeicosatetraenoic Acid Analogs: Antagonism of 20-Hydroxyeicosatetraenoic Acid-Induced Vascular Sensitization and Hypertension. Bioorganic & Medicinal Chemistry Letters, 29 (19), 126616. https://doi.org/10.1016/j.bmcl.2019.08.020