A series of 2-amino-4-aryl-5-oxo-4,5-dihydropyrano[3,2-c]chromene-3-carbonitrile (4a–m) were synthesized via a one-pot three component condensation reaction between 4-hydroxy-2H-chromen-2-one, various aryl aldehydes and malononitrile in the presence of piperidine as a catalyst in ethanol under microwave irradiation conditions, with good to excellent yields. The structure elucidations of all the synthesized compounds were accomplished by spectral data, IR, ¹H NMR, ¹³C NMR, MS, and elemental analyses. The targeted compounds were assessed for their in vitro anticancer activity against mammary gland breast cancer cell line (MCF-7), human colon cancer (HCT-116), and liver cancer (HepG-2) by using sulphorhodamine B assay (SRB) method, while doxorubicin, was utilized as standard reference drug. The cancer cells were treated with the synthesized compounds at differentiable dosages, and cell viability was determined. Compounds 4e, 4f, and 4m exhibited excellent antitumor activity versus all cancer cell lines with IC₅₀ values ranging from 0.2 to 1.7 μM. The cell cycle arrest behavior of compounds 4e, 4f, and 4m was investigated. The results illustrated that the potent cytotoxic compounds 4e, 4f, and 4m induce cell cycle arrest at the G2/M phases and trigger apoptosis in the different tested cancer cells. Finally, the structure activity relationship (SAR) survey highlighted the antitumor activity of the new molecules that was remarkably influenced by the hydrophilicity of certain substituents at certain positions.

中文翻译：

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吡喃并[3,2-c]色烯衍生物的体外抗癌活性同时具有细胞周期阻滞和凋亡诱导作用

通过一锅三组分之间的一锅三组分缩合反应合成了一系列2-氨基-4-芳基-5-氧代-4,5-二氢吡喃[3,2- c ]亚甲基-3-腈（4a – m）。在微波辐射条件下，在乙醇中以哌啶为催化剂，在乙醇中以-羟基-2- H-铬-2--2-酮，各种芳基醛和丙二腈的收率好至极好。所有合成化合物的结构解析均通过光谱数据，红外光谱，¹ H NMR，¹³13 C NMR，MS和元素分析。使用磺基罗丹明B测定（SRB）方法评估了目标化合物对乳腺乳腺癌细胞系（MCF-7），人结肠癌（HCT-116）和肝癌（HepG-2）的体外抗癌活性，将阿霉素用作标准参考药物。用合成化合物以不同剂量处理癌细胞，并测定细胞活力。与所有癌细胞系相比，化合物4e，4f和4m表现出优异的抗肿瘤活性，IC ₅₀值为0.2至1.7μM。化合物4e，4f和4m的细胞周期停滞行为被调查了。结果表明，有效的细胞毒性化合物4e，4f和4m诱导了G2 / M期的细胞周期停滞，并触发了不同测试癌细胞的凋亡。最后，结构活性关系（SAR）调查突出显示了新分子的抗肿瘤活性，该活性受到某些位置某些取代基的亲水性的显着影响。