Chakrapani Harinath, Maciag Anna E, Citro Michael L, Keefer Larry K, Saavedra Joseph E
Chemistry Section, Laboratory of Comparative Carcinogenesis, National Cancer Institute at Frederick, Frederick, Maryland 21702, USA.
Org Lett. 2008 Nov 20;10(22):5155-8. doi: 10.1021/ol8020989. Epub 2008 Oct 29.
Although O(2)-(2,4-dinitrophenyl) derivatives of diazeniumdiolate-based nitric oxide (NO) prodrugs bearing a free carboxylic acid group were activated by glutathione to release NO, these compounds were poor sources of intracellular NO and showed diminished antiproliferative activity against human leukemia HL-60 cells. The carboxylic acid esters of these prodrugs, however, were found to be superior sources of intracellular NO and potent inhibitors of HL-60 cell proliferation.
尽管带有游离羧酸基团的基于连二次硝酸酯的一氧化氮(NO)前药的O(2)-(2,4-二硝基苯基)衍生物可被谷胱甘肽激活以释放NO,但这些化合物是细胞内NO的不良来源,并且对人白血病HL-60细胞的抗增殖活性减弱。然而,这些前药的羧酸酯被发现是细胞内NO的优质来源,也是HL-60细胞增殖的有效抑制剂。