Interaction of the pyridoindole stobadine with peroxyl, superoxide and chromanoxyl radicals.
Interaction of the pyridoindole stobadine with peroxyl, superoxide and chromanoxyl radicals.
复制标题
吡啶并吲哚斯托巴定与过氧自由基、超氧化物自由基和苯并二氢吡喃氧自由基的相互作用。
DOI：
10.1016/0006-2952(93)90075-8
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发表时间：
1993
影响因子：
5.8
通讯作者：
Sies,H
中科院分区：
文献类型：
--
作者：
Kagan,VE;Tsuchiya,M;Serbinova,E;Packer,L;Sies,H
吡啶并吲哚衍生物stobadine [（−）-cis-2，8-dimethyl-2，3，4，4a，5，9 b-hexahydro-1H-pyrido（4，3b）indole]被描述为具有抗缺氧和抗心律失常心脏保护特性的药物。在这里，它与脂质体中的过氧自由基的反应性，使用脂溶性偶氮引发剂的过氧自由基，2，2 '-偶氮-双（2，4-二甲基戊腈）（AMVN），进行了检查。斯托巴丁具有清除作用，可通过抑制（i）顺式-帕里那酸荧光衰减（20μM时的半数最大效应）或（ii）鲁米诺敏化的化学发光（33 μM时的半数最大效应）来证明。在大鼠肝中，μ;在某些情况下，司托巴定在抑制脂溶性（AMVN）或水溶性2，2 '-偶氮-双（2-氨基丙烷）-HCl（AAPH）（过氧自由基的偶氮引发剂）诱导的脂质过氧化方面同样有效，在17 μM时具有半数最大效应。斯托巴丁在正辛醇-水两相体系中的分配系数log P = 0.57 ± 0.03，说明其在脂相和水相中均具有淬灭过氧自由基的能力。Stobadine不是一种有效的超氧自由基清除剂。通过超氧化物诱导的光泽精放大化学发光法测定，司多布定与超氧化物反应的二级速率常数估计为7.5 × 102 M − 1 sec − 1。ESR测量显示，脂质体中的司托巴定不还原具有6-碳侧链的维生素E同系物2，5，7，8-四甲基-2-（4 '-甲基戊基）色满-6-醇（色满醇-α-C6）的色满氧基自由基，这与在均匀溶液中使用Trolox获得的脉冲辐解结果一致（Steenkenet al.，Chem Res Toxicol 5：355-360，1992）。Stobadine增加了由脂氧合酶+花生四烯酸产生的色满氧基和抗坏血酸自由基ESR信号的幅度。这被解释为是由于stobadinyl自由基的相互作用与色原烷醇环和抗坏血酸，分别。这表明，高反应性的司托巴定自由基需要还原性抗氧化剂（维生素E，维生素C）的存在下，表现出其在生理系统中的抗氧化作用。
The pyridoindole derivative stobadine [(−)-cis-2,8-dimethyl-2,3,4,4a,5,9b-hexahydro-1H-pyrido (4,3b)indole] has been described as a drug with antihypoxic and antiarrhythmic cardioprotective properties. Here its reactivity with peroxyl radicals in liposomes using a lipid-soluble azo-initiator of peroxyl radicals, 2,2'-azo-bis(2,4-dimethyl-valeronitrile) (AMVN), was examined. Stobadine exerted scavenging as evidenced by the inhibition of: (i)cis-parinaric acid fluorescence decay (half-maximal effect at 20μM), or (ii) luminol-sensitized chemiluminescence (half-maximal effect at 33 μM). In rat liver mu;somes, stobadine was equally efficient in inhibiting lipid peroxidation induced by lipid-soluble (AMVN) or water-soluble 2,2'-azo-bis(2-aminopropane)-HCl (AAPH), azo-initiators of peroxyl radicals with half-maximal effect at 17 μM. Stobadine partitions in a two-phase system (octanol-water) with the coefficient log P = 0.57 ± 0.03, explaining its ability to quench peroxyl radicals in both lipid and aqueous phases. Stobadine is not an efficient scavenger of Superoxide radicals. The second order rate constant for the reaction of stobadine with Superoxide was estimated to be 7.5 × 102M−1sec−1as measured by superoxide-induced lucigenin-amplified chemiluminescence. ESR measurements showed that stobadine in liposomes does not reduce the chromanoxyl radical of a vitamin E homologue with a 6-carbon side-chain, 2,5,7,8-tetramethyl-2-(4'-methylpentyl)chroman-6-ol (chromanol-α-C6), in agreement with pulse-radiolysis results obtained using Trolox in homogeneous solution (Steenkenet al., Chem Res Toxicol5: 355–360, 1992). Stobadine increased the magnitude of the chromanoxyl and ascorbyl radical ESR signal generated by lipoxygenase + arachidonate. This was interpreted to be due to the interaction of stobadinyl radicals with the chromanol ring and ascorbate, respectively. It is suggested that high reactivity of stobadine radicals requires the presence of reducing antioxidants (vitamin E, vitamin C) to exhibit its antioxidant effects in physiological systems.