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.
authors.affiliation: Department of Chemistry and Biochemistry, University of Arizona, Tucson, Arizona 85721, USA.
authors.forename: Gaurav
authors.initials: G
authors.lastname: Bharadwaj
authors.affiliation: Department of Chemistry and Biochemistry, University of Arizona, Tucson, Arizona 85721, USA.
authors.forename: Patricia G Z
authors.initials: PG
authors.lastname: Benini
authors.affiliation: Department of Chemistry and Biochemistry, University of Arizona, Tucson, Arizona 85721, USA.
authors.forename: Debashree
authors.initials: D
authors.lastname: Basudhar
authors.affiliation: Department of Chemistry and Biochemistry, University of Arizona, Tucson, Arizona 85721, USA.
authors.forename: Cyf N
authors.initials: CN
authors.lastname: Ramos-Colon
authors.affiliation: Department of Chemistry and Biochemistry, University of Arizona, Tucson, Arizona 85721, USA.
authors.forename: Gail M
authors.initials: GM
authors.lastname: Johnson
authors.affiliation: Department of Chemistry and Biochemistry, University of Arizona, Tucson, Arizona 85721, USA.
authors.forename: Marti M
authors.initials: MM
authors.lastname: Larriva
authors.affiliation: Chemical Biology Laboratory, National Cancer Institute at Frederick, Frederick, Maryland 21702, USA.
authors.forename: Larry K
authors.initials: LK
authors.lastname: Keefer
authors.affiliation: Chemical Biology Laboratory, National Cancer Institute at Frederick, Frederick, Maryland 21702, USA.
authors.forename: Daniela
authors.initials: D
authors.lastname: Andrei
authors.affiliation: Department of Chemistry and Biochemistry, University of Arizona, Tucson, Arizona 85721, USA. Electronic address: kmiranda@email.arizona.edu.
authors.forename: Katrina M
authors.initials: KM
authors.lastname: Miranda
mesh_terms: D001391:Azo Compounds / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D009569:Nitric Oxide / Q000378:metabolism*; D013056:Spectrophotometry, Ultraviolet
chemical_list: D001391:Azo Compounds; C452539:diazeniumdiolate; D009569:Nitric Oxide
keywords: Angeli's salt; Diazeniumdiolate; IPA/NO; Nitric oxide; Nitroxyl; Tamoxifen