Department of Chemistry, College of Science, Jouf University, Sakaka 72341, Al Jouf, Saudi Arabia.
Composites and Nanostructured Materials Research Department, Advanced Technology and New Materials Research Institute, City of Scientific Research and Technological Applications (SRTA-City), New Borg Al-Arab, Alexandria 21934, Egypt.
Molecules. 2022 May 4;27(9):2940. doi: 10.3390/molecules27092940.
Herein, a distinctive dihydroxy ionic liquid ([Py-2OH]OAc) was straightforwardly assembled from the sonication of pyridine with 2-chloropropane-1,3-diol by employing sodium acetate as an ion exchanger. The efficiency of the ([Py-2OH]OAc as a promoter for the sono-synthesis of a novel library of condensed products through DABCO-catalyzed Knoevenagel condensation process of adequate active cyclic methylenes and ninhydrin was next investigated using ultimate greener conditions. All of the reactions studied went cleanly and smoothly, and the resulting Knoevenagel condensation compounds were recovered in high yields without detecting the aldol intermediates in the end products. Compared to traditional strategies, the suggested approach has numerous advantages including mild reaction conditions with no by-products, eco-friendly solvent, outstanding performance in many green metrics, and usability in gram-scale synthesis. The reusability of the ionic liquid was also studied, with an overall retrieved yield of around 97% for seven consecutive runs without any substantial reduction in the performance. The novel obtained compounds were further assessed for their in vitro antitumor potential toward three human tumor cell lines: Colo-205 (colon cancer), MCF-7 (breast cancer), and A549 (lung cancer) by employing the MTT assay, and the findings were evaluated with the reference Doxorubicin. The results demonstrated that the majority of the developed products had potent activities at very low doses. Compounds comprising rhodanine () or chromane () moieties exhibited the most promising cytotoxic effects toward three cell lines, particularly rhodanine carboxylic acid derivative (), showing superior cytotoxic effects against the investigated cell lines compared to the reference drug. Furthermore, automated docking simulation studies were also performed to support the results obtained.
本文中，通过吡啶与 2-氯-1,3-丙二醇的超声作用，以醋酸钠作为离子交换剂，简便地组装了一种独特的二羟基离子液体([Py-2OH]OAc)。接下来，在终极绿色条件下，考察了([Py-2OH]OAc 作为 DABCO 催化的活性环状亚甲基和邻苯二酮的 Knoevenagel 缩合反应中新型稠合产物库的超声合成促进剂的效率。研究的所有反应都进行得很顺利，缩合产物以高收率回收，最终产物中没有检测到醛醇中间体。与传统策略相比，所提出的方法具有许多优点，包括无副产物的温和反应条件、环境友好的溶剂、在许多绿色指标上的卓越性能以及在克级合成中的可用性。还研究了离子液体的可重复使用性，在七个连续运行中，总体回收率约为 97%，而性能没有明显下降。进一步通过 MTT 测定法评估了获得的新型化合物对三种人类肿瘤细胞系（结肠癌细胞 Colo-205、乳腺癌 MCF-7 和肺癌 A549）的体外抗肿瘤潜力，并使用参考药物多柔比星进行了评估。结果表明，大多数开发的化合物在非常低的剂量下具有很强的活性。包含绕丹宁()或色满()部分的化合物对三种细胞系表现出最有希望的细胞毒性作用，特别是绕丹宁羧酸衍生物()，对所研究的细胞系的细胞毒性作用优于参考药物。此外，还进行了自动对接模拟研究以支持获得的结果。
