Title: The Nitric Oxide Prodrug JS-K and Its Structural Analogues as Cancer Therapeutic Agents
VOLUME: 9 ISSUE: 7
Author(s):Anna E. Maciag, Joseph E. Saavedra and Harinath Chakrapani
Affiliation:Basic Science Program, SAIC-Frederick, National Cancer Institute at Frederick, Frederick, Maryland 21702, USA and Laboratory of Comparative Carcinogenesis, National Cancer Institute at Frederick, Frederick MD 21702 USA.
Abstract: Nitric oxide (NO) prodrugs of the diazeniumdiolate class are routinely used as reliable sources of nitric oxide in chemical and biological laboratory settings. O2-(2,4-dinitrophenyl) diazeniumdiolates, which are derivatized forms of ionic diazeniumdiolates, have been found to show potent anti-proliferative activity in a variety of cancer cells, presumably through the effects of NO. One important member of this class of diazeniumdiolates, O2-(2,4-dinitrophenyl) 1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate (JS-K), has shown promise as a novel cancer therapeutic agent in a number of animal models. This review describes the developments in chemical and biochemical characterization and structure-activity relationship of JS-K and its analogues. In addition, some molecular mechanistic insights into the observed anti-proliferative activity of JS-K are discussed. Finally, a structural motif is presented for O2-(aryl) diazeniumdiolate nitric oxide prodrugs that show potency comparable with that of JS-K.
