In this study, we applied a direct condensation between 3-acetyl-4-hydroxy-2H-chromen-2-one and different amines (anilines and benzyl amines) in order to synthesize some coumarin-based imines/enamines (3a-o) as cytotoxic agents. All the compounds were characterized by means of FT-IR, NMR, mass spectroscopy and elemental analyses. Since the title compounds can exist as different forms including (s-cis)-imine and (s-trans)-imine or (E and Z)-enamines, their conformational and geometrical aspects were investigated computationally by DFT method. The optimized geometry parameters, ΔE, ΔG, ΔH, Mulliken atomic charge, HOMO and LUMO energy, and NBO analysis suggested that these compounds can exist predominantly in (E)-enamine form. All the synthesized compounds (3a-o) were evaluated in vitro for their cytotoxic activities against cancer cell lines (MCF-7 and A549) and normal cell line (BEAS-2B) using the MTT assay. The 4-hydroxybenzyl derivative 3k was found to be the most potent cytotoxic agent with no selectivity, similar to doxorubicin. However, the 4-chlorobenzyl analog 3o could be considered as an equipotent compound respect to doxorubicin with higher selectivity.

中文翻译：

---

4-羟基香豆素衍生的亚胺/烯胺的合成、计算研究和细胞毒性。

在这项研究中，我们在 3-乙酰基-4-羟基-2H-chromen-2-one 和不同的胺（苯胺和苄胺）之间进行直接缩合，以合成一些基于香豆素的亚胺/烯胺 (3a-o)作为细胞毒剂。所有化合物均通过 FT-IR、NMR、质谱和元素分析进行​​表征。由于标题化合物可以以不同形式存在，包括 (s-cis)-亚胺和 (s-反式)-亚胺或 (E 和 Z)-烯胺，因此通过 DFT 方法计算研究了它们的构象和几何方面。优化的几何参数、ΔE、ΔG、ΔH、马利肯原子电荷、HOMO 和 LUMO 能量以及 NBO 分析表明这些化合物可以主要以 (E)-烯胺形式存在。使用 MTT 测定法在体外评估了所有合成的化合物 (3a-o) 对癌细胞系 (MCF-7 和 A549) 和正常细胞系 (BEAS-2B) 的细胞毒活性。发现 4-羟基苄基衍生物 3k 是最有效的细胞毒性剂，没有选择性，类似于阿霉素。然而，4-氯苄基类似物 3o 可以被认为是与阿霉素等效的化合物，具有更高的选择性。