Analysis of the HNO and NO donating properties of alicyclic amine diazeniumdiolates

Gaurav Bharadwaj, Patricia G Z Benini, Debashree Basudhar, Cyf N. Ramos-Colon, Gail M. Johnson, Marti M. Larriva, Larry K. Keefer, Daniela Andrei, Katrina M Miranda

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Nitroxyl (HNO) donors have been shown to elicit a variety of pharmacological responses, ranging from tumoricidal effects to treatment of heart failure. Isopropylamine-based diazeniumdiolates have been shown to produce HNO on decomposition under physiological conditions. Herein, we report the synthesis and HNO release profiles of primary alicyclic amine-based diazeniumdiolates. These compounds extend the range of known diazeniumdiolate-based HNO donors. Acetoxymethyl ester-protected diazeniumdiolates were also synthesized to improve purification and cellular uptake. The acetoxymethyl derivative of cyclopentylamine diazeniumdiolate not only showed higher cytotoxicity toward cancer cells as compared to the parent anion but was also effective in combination with tamoxifen for targeting estrogen receptor α-negative breast cancer cells.

Original languageEnglish (US)
Pages (from-to)70-78
Number of pages9
JournalNitric Oxide - Biology and Chemistry
Volume42
DOIs
StatePublished - Nov 15 2014

Fingerprint

Amines
Cells
Tamoxifen
Cytotoxicity
Treatment Failure
Estrogen Receptors
Purification
Anions
Esters
Heart Failure
diazeniumdiolate
Pharmacology
Breast Neoplasms
Derivatives
Decomposition
Neoplasms

Keywords

  • Angeli's salt
  • Diazeniumdiolate
  • IPA/NO
  • Nitric oxide
  • Nitroxyl
  • Tamoxifen

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Cancer Research
  • Physiology

Cite this

Bharadwaj, G., Benini, P. G. Z., Basudhar, D., Ramos-Colon, C. N., Johnson, G. M., Larriva, M. M., ... Miranda, K. M. (2014). Analysis of the HNO and NO donating properties of alicyclic amine diazeniumdiolates. Nitric Oxide - Biology and Chemistry, 42, 70-78. https://doi.org/10.1016/j.niox.2014.08.013

Analysis of the HNO and NO donating properties of alicyclic amine diazeniumdiolates. / Bharadwaj, Gaurav; Benini, Patricia G Z; Basudhar, Debashree; Ramos-Colon, Cyf N.; Johnson, Gail M.; Larriva, Marti M.; Keefer, Larry K.; Andrei, Daniela; Miranda, Katrina M.

In: Nitric Oxide - Biology and Chemistry, Vol. 42, 15.11.2014, p. 70-78.

Research output: Contribution to journalArticle

Bharadwaj, G, Benini, PGZ, Basudhar, D, Ramos-Colon, CN, Johnson, GM, Larriva, MM, Keefer, LK, Andrei, D & Miranda, KM 2014, 'Analysis of the HNO and NO donating properties of alicyclic amine diazeniumdiolates', Nitric Oxide - Biology and Chemistry, vol. 42, pp. 70-78. https://doi.org/10.1016/j.niox.2014.08.013
Bharadwaj G, Benini PGZ, Basudhar D, Ramos-Colon CN, Johnson GM, Larriva MM et al. Analysis of the HNO and NO donating properties of alicyclic amine diazeniumdiolates. Nitric Oxide - Biology and Chemistry. 2014 Nov 15;42:70-78. https://doi.org/10.1016/j.niox.2014.08.013
Bharadwaj, Gaurav ; Benini, Patricia G Z ; Basudhar, Debashree ; Ramos-Colon, Cyf N. ; Johnson, Gail M. ; Larriva, Marti M. ; Keefer, Larry K. ; Andrei, Daniela ; Miranda, Katrina M. / Analysis of the HNO and NO donating properties of alicyclic amine diazeniumdiolates. In: Nitric Oxide - Biology and Chemistry. 2014 ; Vol. 42. pp. 70-78.
@article{635b6e7cad114b4980a20a2a4b1bf3eb,
title = "Analysis of the HNO and NO donating properties of alicyclic amine diazeniumdiolates",
abstract = "Nitroxyl (HNO) donors have been shown to elicit a variety of pharmacological responses, ranging from tumoricidal effects to treatment of heart failure. Isopropylamine-based diazeniumdiolates have been shown to produce HNO on decomposition under physiological conditions. Herein, we report the synthesis and HNO release profiles of primary alicyclic amine-based diazeniumdiolates. These compounds extend the range of known diazeniumdiolate-based HNO donors. Acetoxymethyl ester-protected diazeniumdiolates were also synthesized to improve purification and cellular uptake. The acetoxymethyl derivative of cyclopentylamine diazeniumdiolate not only showed higher cytotoxicity toward cancer cells as compared to the parent anion but was also effective in combination with tamoxifen for targeting estrogen receptor α-negative breast cancer cells.",
keywords = "Angeli's salt, Diazeniumdiolate, IPA/NO, Nitric oxide, Nitroxyl, Tamoxifen",
author = "Gaurav Bharadwaj and Benini, {Patricia G Z} and Debashree Basudhar and Ramos-Colon, {Cyf N.} and Johnson, {Gail M.} and Larriva, {Marti M.} and Keefer, {Larry K.} and Daniela Andrei and Miranda, {Katrina M}",
year = "2014",
month = "11",
day = "15",
doi = "10.1016/j.niox.2014.08.013",
language = "English (US)",
volume = "42",
pages = "70--78",
journal = "Nitric Oxide - Biology and Chemistry",
issn = "1089-8603",
publisher = "Academic Press Inc.",

}

TY - JOUR

T1 - Analysis of the HNO and NO donating properties of alicyclic amine diazeniumdiolates

AU - Bharadwaj, Gaurav

AU - Benini, Patricia G Z

AU - Basudhar, Debashree

AU - Ramos-Colon, Cyf N.

AU - Johnson, Gail M.

AU - Larriva, Marti M.

AU - Keefer, Larry K.

AU - Andrei, Daniela

AU - Miranda, Katrina M

PY - 2014/11/15

Y1 - 2014/11/15

N2 - Nitroxyl (HNO) donors have been shown to elicit a variety of pharmacological responses, ranging from tumoricidal effects to treatment of heart failure. Isopropylamine-based diazeniumdiolates have been shown to produce HNO on decomposition under physiological conditions. Herein, we report the synthesis and HNO release profiles of primary alicyclic amine-based diazeniumdiolates. These compounds extend the range of known diazeniumdiolate-based HNO donors. Acetoxymethyl ester-protected diazeniumdiolates were also synthesized to improve purification and cellular uptake. The acetoxymethyl derivative of cyclopentylamine diazeniumdiolate not only showed higher cytotoxicity toward cancer cells as compared to the parent anion but was also effective in combination with tamoxifen for targeting estrogen receptor α-negative breast cancer cells.

AB - Nitroxyl (HNO) donors have been shown to elicit a variety of pharmacological responses, ranging from tumoricidal effects to treatment of heart failure. Isopropylamine-based diazeniumdiolates have been shown to produce HNO on decomposition under physiological conditions. Herein, we report the synthesis and HNO release profiles of primary alicyclic amine-based diazeniumdiolates. These compounds extend the range of known diazeniumdiolate-based HNO donors. Acetoxymethyl ester-protected diazeniumdiolates were also synthesized to improve purification and cellular uptake. The acetoxymethyl derivative of cyclopentylamine diazeniumdiolate not only showed higher cytotoxicity toward cancer cells as compared to the parent anion but was also effective in combination with tamoxifen for targeting estrogen receptor α-negative breast cancer cells.

KW - Angeli's salt

KW - Diazeniumdiolate

KW - IPA/NO

KW - Nitric oxide

KW - Nitroxyl

KW - Tamoxifen

UR - http://www.scopus.com/inward/record.url?scp=84908274691&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84908274691&partnerID=8YFLogxK

U2 - 10.1016/j.niox.2014.08.013

DO - 10.1016/j.niox.2014.08.013

M3 - Article

VL - 42

SP - 70

EP - 78

JO - Nitric Oxide - Biology and Chemistry

JF - Nitric Oxide - Biology and Chemistry

SN - 1089-8603

ER -