Nitroxyl analogs as inhibitors of aldehyde dehydrogenase. C-nitroso compounds.
Nitroxyl analogs as inhibitors of aldehyde dehydrogenase. C-nitroso compounds.
复制标题
硝酰基类似物作为醛脱氢酶的抑制剂。
DOI：
10.1016/0006-2952(93)90026-s
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发表时间：
1993
影响因子：
5.8
通讯作者：
DeMaster,EG
中科院分区：
文献类型：
--
作者：
Nagasawa,HT;Yost,Y;Elberling,JA;Shirota,FN;DeMaster,EG
We previously postulated that the catalase-mediated oxidation of cyanamide leads to the formation of the unstable intermediate,N-hydroxycyanamide, which spontaneously decomposes to nitroxyl, the putative inhibitor of aldehyde dehydrogenase (EC 1.2.1.3; AlDH). Since it was not possible to provide direct evidence for the inhibition of AlDH by nitroxyl, we examined the activity of three representative substituted nitroxyls (C-nitroso compounds), viz. nitrosobenzene (NB), 1-nitroso-adamantane (NA), and 2-methyl-2-nitrosopropane (MNP), as direct inhibitors of yeast A1DHin vitro. While NB and NA were highly effective inhibitors in this system exhibiting IC50values of 2.5 and 8.6 μM, respectively, MNP was considerably less effective with an IC50of 0.15 mM. When testedin vivo, NA did not show any inhibitory activity on the hepatic AlDH, possibly due to the lack of site-specific delivery of the active monomeric form of this compound. However, NB at a low dose did inhibit hepatic AlDH as reflected by an increase in blood acetaldehyde levels. These results attest to the abilities of NB and NA to act as direct inhibitors of A1DH analogous to nitroxyl itself.
