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

•Primary alicyclic amine-based diazeniumdiolates function as HNO donors.•These compounds extend the range of known diazeniumdiolate-based HNO donors.•An acetoxymethyl ester derivative showed higher cytotoxicity toward cancer cells.•This derivative is also effective in tandem with tamoxifen against breast cancer cells. 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.