Altowyan Mezna Saleh, Soliman Saied M, Haukka Matti, Al-Shaalan Nora Hamad, Alkharboush Aminah A, Barakat Assem
Department of Chemistry, College of Science, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia.
Department of Chemistry, Faculty of Science, Alexandria University, P.O. Box 426, Ibrahimia, Alexandria 21321, Egypt.
ACS Omega. 2022 Sep 27;7(40):35743-35754. doi: 10.1021/acsomega.2c03790. eCollection 2022 Oct 11.
A new series of spirooxindoles based on ethylene derivatives having furan aryl moiety are reported. The new hybrids were achieved via [3 + 2] cycloaddition reaction as an economic one-step efficient approach. The final constructed spirooxindoles have four contiguous asymmetric carbon centers. The structure of is exclusively confirmed using X-ray single crystal diffraction. The supramolecular structure of is controlled by O···H, H···H, and C···C intermolecular contacts. It includes layered molecules interconnected weak C-H···O (2.675 Å), H···H (2.269 Å), and relatively short Cl···Br interhalogen interactions [3.4500(11)Å]. Using Hirshfeld analysis, the percentages of these intermolecular contacts are 10.6, 25.7, 6.4, and 6.2%, respectively. The spirooxindoles along with ethylene derivatives having furan aryl moiety were assessed against breast (MCF7) and liver (HepG2) cancer cell lines. The results indicated that the new chalcone showed excellent activity in both cell lines (MCF7 and HepG2) with IC = 4.1 ± 0.10 μM/mL (MCF7) and 3.5 ± 0.07 μM/mL (HepG2) compared to staurosporine with 4.3 and 2.92 folds. Spirooxindoles (IC = 4.3 ± 0.18 μM/mL), (IC = 10.3 ± 0.40 μM/mL), (IC = 10.7 ± 0.38 μM/mL), and (IC = 4.7 ± 0.18 μM/mL) exhibited potential activity against breast adenocarcinoma, while compounds (IC = 6.9 ± 0.23 μM/mL) and (IC = 3.5 ± 0.11 μM/mL) were the most active hybrids against human liver cancer cell line (HepG2) compared to staurosporine [IC = 17.8 ± 0.50 μM/mL (MCF7) and 10.3 ± 0.23 μM/mL (HepG2)]. Molecular docking study exhibited the virtual mechanism of binding of compound as a dual inhibitor of EGFR/CDK-2 proteins, and this may highlight the molecular targets for its cytotoxic activity.
报道了一系列基于具有呋喃芳基部分的乙烯衍生物的新型螺环氧化吲哚。通过[3 + 2]环加成反应实现了这些新型杂化物的合成，这是一种经济的一步高效方法。最终构建的螺环氧化吲哚具有四个相邻的不对称碳中心。通过X射线单晶衍射专门确定了其结构。其超分子结构由O···H、H···H和C···C分子间相互作用控制。它包括通过弱C - H···O（2.675 Å）、H···H（2.269 Å）和相对较短的Cl···Br卤间相互作用[3.4500(11)Å]相互连接的层状分子。使用Hirshfeld分析，这些分子间相互作用的百分比分别为10.6%、25.7%、6.4%和6.2%。对具有呋喃芳基部分的螺环氧化吲哚以及乙烯衍生物针对乳腺癌（MCF7）和肝癌（HepG2）细胞系进行了评估。结果表明，新型查耳酮在两种细胞系（MCF7和HepG2）中均表现出优异的活性，其IC50 = 4.1 ± 0.10 μM/mL（MCF7）和3.5 ± 0.07 μM/mL（HepG2），与星形孢菌素相比分别有4.3倍和2.92倍的优势。螺环氧化吲哚（IC50 = 4.3 ± 0.18 μM/mL）、（IC50 = 10.3 ± 0.40 μM/mL）、（IC50 = 10.7 ± 0.38 μM/mL）和（IC50 = 4.7 ± 0.18 μM/mL）对乳腺腺癌表现出潜在活性，而化合物（IC50 = 6.9 ± 0.23 μM/mL）和（IC = 3.5 ± 0.11 μM/mL）与星形孢菌素相比[IC50 = 17.8 ± 0.50 μM/mL（MCF7）和10.3 ± 0.23 μM/mL（HepG2）]是针对人肝癌细胞系（HepG2）最具活性的杂化物。分子对接研究展示了化合物作为EGFR/CDK - 2蛋白双重抑制剂的虚拟结合机制，这可能突出了其细胞毒性活性的分子靶点。
