Abstract

The design and microwave-assisted synthesis of four series (IIIa–IIIo, Va–Vg, VIIa–VIIg and IXa–IXe) of mono and bis-amide derivatives of ferulic acid have been achieved under solvent-free conditions and, subsequently characterized by spectroscopic techniques. During thermal analysis, all the compounds were found stable up to 100 °C and decomposed through single step at higher temperature. The derivatives were screened for their in vitro cytotoxicity and antioxidant activity, respectively and observed that compound Vb was most active against breast (MCF-7; IC₅₀ = 07.49 µM and MDA-MB-231; IC₅₀ = 07.28 µM), Vd against lung (A549; IC₅₀ = 07.11 µM) and liver (HepG2; IC₅₀ = 08.32 µM), and Ve against cervical (HeLa; IC₅₀ = 07.14 µM) cancer cell lines, while compounds IIIf, IIIl, IIIo, VIIe and IXa–IXe were found to exhibit the strong antioxidant activity with respect to their parent molecule. Previous reports for the biological applications of ferulic acid amides also confirmed the importance of work presented here. The 3D-QSAR studies for anticancer and antioxidant activities were also performed by using CoMFA, and the corresponding contour maps of electrostatic and steric fields have been computed. Statistical analysis between experimental and CoMFA-predicted data for pIC₅₀ have been accomplished by curve fitting analysis which showed the significant correlation.

Graphical Abstract

中文翻译：

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阿魏酸酰胺衍生物作为抗癌剂和抗氧化剂：合成，热，生物学和计算研究

摘要

在无溶剂条件下完成了阿魏酸单酰胺和双酰胺衍生物的四个系列（IIIa–IIIo，Va–Vg，VIIa–VIIg和IXa–IXe）的设计和微波辅助合成，其特征在于光谱技术。在热分析过程中，发现所有化合物在高达100°C的温度下均稳定，并在较高的温度下通过一步分解。分别对衍生物的体外细胞毒性和抗氧化活性进行了筛选，观察到化合物Vb对乳房的活性最高（MCF-7； IC ₅₀  = 07.49 µM和MDA-MB-231； IC ₅₀  = 07.28 µM），Vd对乳房最有效。肺（A549； IC ₅₀ = 07.11μM）和肝（HepG2细胞; IC ₅₀  = 08.32μM）和Ve的免受子（HeLa细胞; IC ₅₀  = 07.14μM）癌细胞系，而化合物IIIF，IIIL，IIIO，VIIE和IXA-IXE发现显示相对于其母体分子具有很强的抗氧化活性。先前关于阿魏酰胺的生物学应用的报道也证实了本文提出的工作的重要性。还使用CoMFA进行了抗癌和抗氧化活性的3D-QSAR研究，并计算了相应的静电场和空间场等高线图。pIC _50的实验数据与CoMFA预测数据之间的统计分析 通过曲线拟合分析已经完成，显示出显着的相关性。

图形概要