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

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, J R Falck

Biochemistry

Research output: Contribution to journal › Article

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

Fingerprint Dive into the research topics of '19-Hydroxyeicosatetraenoic acid analogs: Antagonism of 20-hydroxyeicosatetraenoic acid-induced vascular sensitization and hypertension'. Together they form a unique fingerprint.

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), [126616]. https://doi.org/10.1016/j.bmcl.2019.08.020

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 journal › Article

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.

@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, {J R}",

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, J 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

VL - 29

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

SN - 0960-894X

IS - 19

M1 - 126616

ER -