A new series of tetrahydroquinoline-isoxazoline hybrid derivatives (3a–p) were efficiently synthesized involving 1,3-dipolar cycloaddition reaction according to click chemistry approach, from the corresponding N-allyl-4-(2-oxopyrrolinidyl-1)-tetrahydroquinolines preformed, with moderate to good yields (63–77%). To establish new candidates with anticancer activity, the antiproliferative effect of these compounds was measured by the MTT assay on different cancer cell lines such as human breast adenocarcinoma (MCF-7), human liver carcinoma (HepG2), human lung adenocarcinoma (A549), cervical cancer (HeLa), and murine melanoma (B16F10). Compounds 3a (CC₅₀ = 11.37 μM, SI = 5.1) and 3i (CC₅₀ = 25.59 μM, SI > 4.6) showed the best anticancer activities against murine melanoma cells with considerable selectivity compared with VERO cells. Compound 3h showed the best anticancer activity on cervical cancer (HeLa) cells (CC₅₀ = 10.21 μM, SI = 4.1), and it was also slightly more active than the reference drug oxaliplatin. In addition, the compounds 3a and 3m decrease the mitochondrial membrane potential and induce apoptosis, suggesting that their cytotoxic effects may be based on mitochondrial parameter modulation.

中文翻译：

---

束缚于异恶唑啉部分的新四氢喹啉杂合物的合成及抗癌活性

根据点击化学方法，从相应的N-烯丙基-4-（2-氧吡咯啉基-1）-四氢喹啉中，按照点击化学方法，有效合成了一系列新的四氢喹啉-异恶唑啉杂化衍生物（3a-p），涉及1,3-偶极环加成反应。 ，收益率中等至良好（63–77％）。为了建立具有抗癌活性的新候选物，通过MTT分析法测量了这些化合物对不同癌细胞系（例如人乳腺腺癌（MCF-7），人肝癌（HepG2），人肺腺癌（A549），子宫颈癌（HeLa）和鼠类黑色素瘤（B16F10）。化合物3a（CC ₅₀  = 11.37μM，SI = 5.1）和3i（CC ₅₀ = 25.59μM，SI> 4.6）对小鼠黑色素瘤细胞具有最好的抗癌活性，与VERO细胞相比具有相当高的选择性。化合物3h对宫颈癌（HeLa）细胞表现出最佳的抗癌活性（CC ₅₀  = 10.21μM，SI = 4.1），并且其活性也比参考药物奥沙利铂稍高。另外，化合物3a和3m降低线粒体膜电位并诱导细胞凋亡，表明它们的细胞毒性作用可能基于线粒体参数调节。