Phenolic furanochromene hydrazone derivatives: Synthesis, antioxidant activity, ferroptosis inhibition, DNA cleavage and DNA molecular docking studies
Phenolic furanochromene hydrazone derivatives: Synthesis, antioxidant activity, ferroptosis inhibition, DNA cleavage and DNA molecular docking studies
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酚醛呋喃色烯腙衍生物：合成、抗氧化活性、铁死亡抑制、DNA 裂解和 DNA 分子对接研究
DOI：
10.1016/j.bmc.2022.117088
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发表时间：
2022
影响因子：
3.5
通讯作者：
Henry, Geneive E.
中科院分区：
文献类型：
--
作者：
Saylor, Jessica L.;Basile, Olivia N.;Li, Huifang;Hunter, Lindsey M.;Weaver, Ashton;Shellenberger, Blake M.;Ann Tom, Lou;Ma, Hang;Seeram, Navindra P.;Henry, Geneive E.
设计并合成了二十四种酚类呋喃苯色烯腙衍生物，以评估一系列抗氧化剂相关测定中的结构-活性关系。这些衍生物在苯酚环上具有不同的取代模式，一些化合物具有一个、两个或三个羟基，而其他化合物则含有一个羟基与甲氧基、甲基、溴、碘和/或硝基的组合。使用 DPPH 自由基清除和 CUPRAC 测定法测定抗氧化活性。含有邻二羟基和对二羟基模式的化合物具有最高的自由基清除活性，IC50 值范围为 5.0 至 28 μM。同样，具有邻二羟基和对二羟基模式的衍生物，以及 4-羟基-3,5-二甲氧基模式，以 Trolox 作为标准，显示出强大的铜 (II) 离子还原能力。这些衍生物的 Trolox 当量抗氧化能力 (TEAC) 系数范围为 1.75 至 3.97。作为抗氧化潜力的进一步证据，超过一半的衍生物逆转了 HaCaT 细胞中erastin诱导的铁死亡。此外，其中 23 种衍生物在 1 mM 铜 (II) 离子存在下可有效切割超螺旋质粒 DNA，其中 3,4-二羟基衍生物在 3.9 uM 时可切割线性和开放环状形式。分子对接研究证实了酚类呋喃色烯衍生物与DNA的相互作用，结果表明所有衍生物都有利地结合在DNA的小沟中。
Twenty-four phenolic furanochromene hydrazone derivatives were designed and synthesized in order to evaluate structure–activity relationships in a series of antioxidant-related assays. The derivatives have varying substitution patterns on the phenol ring, with some compounds having one, two or three hydroxy groups, and others containing one hydroxy group in combination with methoxy, methyl, bromo, iodo and/or nitro groups. Antioxidant activity was determined using the DPPH free radical scavenging and CUPRAC assays. Compounds containingortho-dihydroxy andpara-dihydroxy patterns had the highest free radical scavenging activity, with IC50values ranging from 5.0 to 28 μM. Similarly, derivatives withortho-dihydroxy andpara-dihydroxy patterns, together with a 4-hydroxy-3,5‑dimethoxy pattern, displayed strong copper (II) ion reducing capacity, using Trolox as a standard. Trolox equivalent antioxidant capacity (TEAC) coefficients for these derivatives ranged from 1.75 to 3.97. As further evidence of antioxidant potential, greater than half of the derivatives reversed erastin-induced ferroptosis in HaCaT cells. In addition, twenty-three of the derivatives were effective at cleaving supercoiled plasmid DNA in the presence of copper (II) ions at 1 mM, with the 3,4‑dihydroxy derivative showing cleavage to both the linear and open circular forms at 3.9 uM. The interaction of the phenolic furanochromene derivatives with DNA was confirmed by molecular docking studies, which revealed that all the derivatives bind favorably in the minor groove of DNA.