Effect of N-Amide Substitution on Antioxidative Activities of Melatonin Derivatives
Effect of N-Amide Substitution on Antioxidative Activities of Melatonin Derivatives
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DOI：
10.3390/scipharm88010003
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发表时间：
2020-03-01
影响因子：
2.5
通讯作者：
Puthongking, Ploenthip
中科院分区：
文献类型：
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作者：
Panyatip, Panyada;Johns, Nutjaree Pratheepawanit;Puthongking, Ploenthip
合成了5个N-酰胺取代的褪黑激素（MLT）衍生物，并对其抗氧化活性进行了评价，其中化合物9-12的ESR响应比MLT高。4-在芬顿反应中，溴苯甲酰基和萘甲酰基衍生物（10和11）对羟自由基的抑制作用强于MLT。在MLT核心结构上的N1-位被乙酰基（8）、苯甲酰基（9）、4-溴苯甲酰基（10）和萘甲酰基（11）取代，以及被4-溴苯甲酰基（12）取代的N2-位降低了衍生物在铁还原抗氧化能力（FRAP）测定中的还原能力。化合物8-11在2，2 '-连氮基双（3-乙基苯并噻唑啉-6-磺酸）二钠盐（ABTS）测定中也表现出比它们的母体化合物更低的抗氧化能力;而化合物12表现出与MLT类似的自由基清除活性。所有芳基衍生物（9-12）显示出比MLT高约三倍的淬灭过氧自由基的能力，尤其是苯甲酰化衍生物（9和10），其在氧自由基吸收能力（ORAC）测定中表现出最高的能力。
Five N-amide substituted melatonin (MLT) derivatives were synthesized and evaluated for antioxidative activities, and compounds 9-12 showed higher electron spin resonance (ESR) response than MLT. 4-Bromobenzoyl and naphthoyl derivatives (10 and 11) presented stronger hydroxyl radical inhibitory effect than MLT in Fenton reaction. The substitution at the N1-position on the MLT core structure with acetyl (8), benzoyl (9), 4-bromobenzoyl (10), and naphthoyl (11) and N2-substitution with 4-bromobenzoyl (12) decreased the reducing power of the derivatives in ferric reducing antioxidant power (FRAP) assay. Compounds 8-11 also presented lower antioxidant capacity than their parent compound in 2,2 '-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) disodium salt (ABTS) assay; whereas, compound 12 presented radical scavenging activity similarly to MLT. All aryl derivatives (9-12) showed higher ability to quench peroxyl radicals than MLT about three times, especially the benzoylated derivatives (9 and 10) that presented the highest ability in oxygen radical absorbance capacity (ORAC) assay.