鲁兹锥体dihydrolipoamide吩噻嗪阳离子自由基脱氢酶作为目标。抗氧化剂的效果。

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Gutierrez-Correa J

鲁兹锥体dihydrolipoamide吩噻嗪阳离子自由基脱氢酶作为目标。抗氧化剂的效果。

咕咕叫药物靶点。2006年9月,7 (9):1155 - 79。

PubMed ID

17017892 (在PubMed

]

文摘

髓过氧化酶(MPO),肌红蛋白(Mb)和辣根过氧化物酶(合)催化生成的单电子氧化radical-cations吩噻嗪类(PTZ)。这些激进分子的瞬态的形成(PTZ +)证实了ESR和光学光谱。这些物种正朝着鲁兹锥体LADH活性(t . cruzi LADH), t . cruzi trypanothione还原酶(t . cruzi TR)和可能的其他高分子的目标。t . cruzi酶都不可逆转地灭活。t . cruzi LADH失活取决于:1)PTZ结构、过氧化物酶的性质和生产速度PTZ +。激进的阳离子;b)孵化时间;c)拦截自由基的抗氧化剂的存在。PTZ +的生产。激进的阳离子,是至关重要的t . cruzi LADH失活,与电子供体基质的能力,合格的哈米特sigmapara常数的subtituent PTZ第二”的位置。 Promazine (PZ), trimeprazine (TMPZ) and thioridazine (TRDZ) were the most effective inactivating agents, whereas trifluophenothiazines with CF3 group at 2-position (Trifluoperazine (TFP), fluphenazine (FFZ) and trifluopromazine (TFPZ)), and propericyazine (PCYZ) with CN group at 2-position, were much less active or inactive, all in close agreement with their higher or lowest electron donor ability, respectively. Comparison of inactivation values for T. cruzi LADH and mammalian heart LADH demonstrated a greater sensitivity of T. cruzi LADH to various PTZ studied. Thiol compounds, tyrosine, dopa, tryptophan, NADH, ascorbate and trolox prevented T. cruzi LADH inactivation by the peroxidase/H2O2 systems in agreement with their ability to suppress PTZ+. radical cations. The role of these radicals as enzyme inhibitors, or as generators of secondary free radicals and metabolite depletors may contribute to explain the trypanocidal effect as well as other chemotherapeutic actions of PTZ.

DrugBank数据引用了这篇文章

药物靶点

药物	目标	类	生物	药理作用	行动
NADH	Dihydrolipoyl脱氢酶、线粒体	蛋白质	人类	未知的	不可用	细节