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

doi:10.1016/j.bmcl.2019.08.020

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

Biochemistry

Research output: Contribution to journal › Article › peer-review

9 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 language	English (US)
Article number	126616
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	29
Issue number	19
DOIs	https://doi.org/10.1016/j.bmcl.2019.08.020
State	Published - 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

Access to Document

10.1016/j.bmcl.2019.08.020

Cite this

Dakarapu, R., Errabelli, R., Manthati, V. L., Michael Adebesin, A., Barma, D. K., Barma, D., Garcia, V., Zhang, F., Laniado Schwartzman, M., & Falck, J. R. (2019). 19-Hydroxyeicosatetraenoic acid analogs: Antagonism of 20-hydroxyeicosatetraenoic acid-induced vascular sensitization and hypertension. Bioorganic and Medicinal Chemistry Letters, 29(19), Article 126616. https://doi.org/10.1016/j.bmcl.2019.08.020

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

@article{2b7578e47fce436cb44f319402fdf770,

title = "19-Hydroxyeicosatetraenoic acid analogs: Antagonism of 20-hydroxyeicosatetraenoic acid-induced vascular sensitization and hypertension",

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.",

keywords = "Antagonist, Bioisosteric replacement, Eicosanoid, Hypertension, QDEGARKRKXEQDF-AAHZGTINSA-M, Vascular sensitization",

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

note = "Publisher Copyright: {\textcopyright} 2019 Elsevier Ltd",

year = "2019",

month = oct,

day = "1",

doi = "10.1016/j.bmcl.2019.08.020",

language = "English (US)",

volume = "29",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

publisher = "Elsevier Limited",

number = "19",

}

TY - JOUR

T1 - 19-Hydroxyeicosatetraenoic acid analogs

T2 - Antagonism of 20-hydroxyeicosatetraenoic acid-induced vascular sensitization and hypertension

AU - Dakarapu, Rambabu

AU - Errabelli, Ramu

AU - Manthati, Vijaya L.

AU - Michael Adebesin, Adeniyi

AU - Barma, Deb K.

AU - Barma, Deepan

AU - Garcia, Victor

AU - Zhang, Fan

AU - Laniado Schwartzman, Michal

AU - Falck, John R.

PY - 2019/10/1

Y1 - 2019/10/1

N2 - 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.

AB - 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.

KW - Antagonist

KW - Bioisosteric replacement

KW - Eicosanoid

KW - Hypertension

KW - QDEGARKRKXEQDF-AAHZGTINSA-M

KW - Vascular sensitization

UR - http://www.scopus.com/inward/record.url?scp=85070704651&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85070704651&partnerID=8YFLogxK

U2 - 10.1016/j.bmcl.2019.08.020

DO - 10.1016/j.bmcl.2019.08.020

M3 - Article

C2 - 31439380

AN - SCOPUS:85070704651

SN - 0960-894X

VL - 29

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 19

M1 - 126616

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this