Novel 6-formylpterin derivatives: chemical synthesis and O2 to ROS conversion activities.
Novel 6-formylpterin derivatives: chemical synthesis and O2 to ROS conversion activities.
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新型 6-甲酰蝶呤衍生物：化学合成和 O2 到 ROS 的转化活性。
DOI：
10.1039/b602778d
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发表时间：
2006
影响因子：
3.2
通讯作者：
K. Makino
中科院分区：
文献类型：
--
作者：
Mitsuru Nonogawa;T. Arai;N. Endo;S. Pack;T. Kodaki;K. Makino
6-甲酰蝶呤（6 FP）对沙土鼠短暂性脑缺血再灌注损伤具有明显的神经保护作用。此外，已经表明，在大鼠中，6 FP保护视网膜神经元，即使在缺血性损伤后施用。由于存在对有效抑制由缺氧供应引起的事件的这种化合物的显著需求，6 FP吸引了进一步的研究。然而，不幸的是，由于其自组装能力，6 FP在中性pH下几乎不溶于水和有机溶剂中。虽然在碱性水中可以得到几mM的6 FP溶液，但它是不稳定的。在本研究中，已经开发了一种新的6 FP的化学衍生化，其保持6 FP的6-位上的甲酰基，这是6 FP的生理活性所必需的，并增加在水和有机溶剂中的溶解度。在该方法中，6 FP的2-和3-位通过三组分偶联反应进行修饰：6 FP与酰氯和N，N-二甲基甲酰胺进行反应。此处合成的衍生物，2-（N，N-二甲基氨基亚甲基氨基）-6-甲酰基-3-新戊酰基蝶啶-4-酮1，2-（N，N-二甲基氨基亚甲基氨基）-6-甲酰基-3-异丁酰基蝶啶-4-酮2和2-（N，N-二甲基氨基亚甲基氨基）-6-甲酰基-3-邻甲苯酰基蝶啶-4-酮3，在水（1.0- 5.6mM）和有机溶剂中显示出高溶解度。还确定了导数1的O（2）转换性质。使用氧电极，已经发现，O（2）在1和NADH存在下在pH 7.4左右被消耗，并且O（2）消耗的速率通过UV-A照射而增强。结合DMPO自旋捕获的电子顺磁共振（EPR）分析也表明，在NADH存在下，1将O（2）转化为O（2）（-），O（2）（-）进一步还原为OH。在类似体系中，通过UV-A照射，观察到（1）O（2）的形成。这些结果与先前报道的6 FP相似。
6-Formylpterin (6FP) has been demonstrated to have strong neuroprotective effects against transient ischemia-reperfusion injury in gerbils. Also it has been shown that in rats, 6FP protected retinal neurons even when it was administered after the ischemic insult. Since there is a significant need for such a compound that effectively suppresses the events caused by the lack of oxygen supply, 6FP has attracted further investigation. Unfortunately, however, 6FP is hardly soluble in water at neutral pH and in organic solvents because of its self-assembling ability. Although a several mM solution of 6FP is available in alkaline water, it is unstable. In the present study, a novel chemical derivatization of 6FP has been developed which maintains the formyl group on the 6-position of 6FP, which is essential for the physiological activities of 6FP, and increases solubility in water and organic solvents. In the method, the 2- and 3-positions of 6FP were modified by a three component coupling reaction: 6FP was subjected to the reaction with acid chloride and N,N-dimethylformamide. The derivatives synthesized here, 2-(N,N-dimethylaminomethyleneamino)-6-formyl-3-pivaloylpteridine-4-one 1, 2-(N,N-dimethylaminomethyleneamino)-6-formyl-3-isobutyrylpteridine-4-one 2, and 2-(N,N-dimethylaminomethyleneamino)-6-formyl-3-o-toluoylpteridine-4-one 3, showed high solubility in water (1.0-5.6 mM) and organic solvents. The O(2) conversion property has also been determined for the derivative 1. Using an oxygen electrode, it has been found that O(2) is consumed in the presence of 1 and NADH at around pH 7.4 and that the rate of O(2) consumption is enhanced by UV-A irradiation. Electron paramagnetic resonance (EPR) analysis coupled with DMPO spin trapping has also revealed that in the presence of NADH, 1 converts O(2) to O(2)(-), which is further reduced to OH. By UV-A illumination in the analogous systems, (1)O(2) formation was observed. These results are similar to those reported previously for 6FP.
影响因子：
4
作者：
A. Oller;C. Buser;M. Tyo;W. Thilly
通讯作者：
A. Oller;C. Buser;M. Tyo;W. Thilly
影响因子：
5
作者：
Lee, JW;Miyawaki, H;Bobst, AM
通讯作者：
Bobst, AM
影响因子：
7.4
作者：
Maulik, N;Yoshida, T;Das, DK
通讯作者：
Das, DK