The Nitric Oxide Prodrug JS-K and Its Structural Analogues as Cancer Therapeutic Agents

Anna   E.   Maciag; Joseph   E.   Saavedra; Harinath      Chakrapani

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.

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