Glazer R I, Hartman K D, Knode M C, Richard M M, Chiang P K, Tseng C K, Marquez V E
Biochem Biophys Res Commun. 1986 Mar 13;135(2):688-94. doi: 10.1016/0006-291x(86)90048-3.
3-Deazaneplanocin, a new carbocyclic analog of adenosine, was synthesized as an inhibitor of S-adenosylhomocysteine hydrolase. The Ki of 3-deazaneplanocin for a purified hamster liver preparation of S-adenosylhomocysteine hydrolase was 5 X 10(-11) M, making this inhibitor 250-fold more potent than the previously known most potent inhibitor of this enzyme, 3-deazaaristeromycin. Inhibition was competitive with the substrate adenosine. Human promyelocytic leukemia (HL-60) cells treated with 10(-5) M 3-deazaneplanocin showed a pronounced elevation in S-adenosylhomocysteine which was 4-fold greater than that produced by an equimolar concentration of 3-deazaaristeromycim. This effect preceded a moderate reduction in cell growth and viability following continuous exposure for 6 days. Cellular differentiation as monitored by the reduction of nitroblue tetrazolium was not markedly affected except after 4 days exposure to 10(-5) M 3-deazaneplanocin where 60% of the viable cells were positive. These results indicate that 3-deazaneplanocin may have therapeutic potential as an anticancer or antiviral drug.
3 - 去氮泽连诺辛，一种新的腺苷碳环类似物，被合成作为S - 腺苷同型半胱氨酸水解酶的抑制剂。3 - 去氮泽连诺辛对纯化的仓鼠肝脏S - 腺苷同型半胱氨酸水解酶制剂的Ki为5×10⁻¹¹ M，使该抑制剂比该酶先前已知的最有效抑制剂3 - 去氮阿糖胞苷菌素的效力高250倍。抑制作用与底物腺苷竞争。用10⁻⁵ M 3 - 去氮泽连诺辛处理的人早幼粒细胞白血病（HL - 60）细胞显示S - 腺苷同型半胱氨酸显著升高，比等摩尔浓度的3 - 去氮阿糖胞苷菌素产生的升高高4倍。在连续暴露6天后，这种效应先于细胞生长和活力的适度降低。通过硝基蓝四氮唑还原监测的细胞分化没有受到明显影响，除非在暴露于10⁻⁵ M 3 - 去氮泽连诺辛4天后，此时60%的活细胞呈阳性。这些结果表明，3 - 去氮泽连诺辛作为抗癌或抗病毒药物可能具有治疗潜力。
