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Forum on Immunopathological Diseases and Therapeutics

ISSN Print: 2151-8017
ISSN Online: 2151-8025

Forum on Immunopathological Diseases and Therapeutics

DOI: 10.1615/ForumImmunDisTher.v1.i3.30
pages 205-218

Broad-Spectrum Anti-Cancer Activity of O2-Arylated Diazeniumdiolates

Larry K. Keefer
Chemical Biology Laboratory, Frederick National Laboratory for Cancer Research, Frederick, Maryland

ABSTRACT

O2-(2,4-Dinitrophenyl) l-[(4-ethoxycarbonyl)piperazin-l-yl]diazen-l-ium-l,2-diolate (JS-K) and O2-{2,4-dinitro-5-[4-(N-methylammo)be nzoyloxy]phenyl} l-(N,N-dimethylamino)diazen-l-ium-l,2-diolate (PABA/NO) are O2-arylated diazeniumdiolates that have shown promising in vivo activity in a variety of rodent cancer models, including prostate cancer, leukemia, liver cancer, multiple myeloma, and ovarian cancer. This compound class was designed to be activated for anti-cancer effects by glutathione-S-transferase (GST)-induced release of cytotoxic nitric oxide (NO), but mechanistic studies have implicated a variety of pathways, some GST/NO-related, some not. Current work is focused on improving formulations and other drug development activities, as well as exploring possible new applications of these agents and their analogs. The selectivity of these drugs for attacking tumors while exhibiting little toxicity toward normal tissues suggests considerable promise for the treatment of various tumor types.