Department of Chemistry, College of Science, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi Arabia.
J Biomol Struct Dyn. 2023;41(24):15009-15022. doi: 10.1080/07391102.2023.2187222. Epub 2023 Mar 16.
Novel series of 2-oxindoline hydrazones , 3-hydroxy-2-oxoindolines and 2-oxoindolin-3-ylidenes were prepared and assessed for their anticancer activity towards breast cancer cell line (MCF7). Compounds , , , , and (IC = 14.0 ± 0.7, 15.6 ± 0.7, 13.8 ± 0.7, 4.9 ± 0.2, 6.0 ± 0.3 and 10.8 ± 0.5 µM, respectively) showed the highest growth inhibition activity against MCF7 when compared to staurosporine (IC = 14.5 ± 0.7 µM). Cell cycle analysis exposed arrest at G1 phase for compounds , and , at S phase for compounds and , and at G1/S phase for compound . Apoptotic effect of compounds , , , , and was confirmed their early and late apoptotic effects. A safety profile was revealed for compounds , , , , and on MCF10A treated normal cell. Also, compounds and displayed a promising CDK2 inhibition activity (IC = 0.22 ± 0.01, 0.25 ± 0.01 µM, respectively). Also, docking study revealed comparable interactions with the native ligand (5-bromoindirubin). ADMET computational studies forecast the promising pharmacokinetic profile of the targeted compounds.Communicated by Ramaswamy H. Sarma.
新型 2-氧代吲哚啉腙、3-羟基-2-氧代吲哚啉和 2-氧代吲哚啉-3-亚烯类化合物被制备出来，并评估了它们对乳腺癌细胞系（MCF7）的抗癌活性。与 staurosporine（IC=14.5±0.7µM）相比，化合物 、 、 、 、 和 （IC=14.0±0.7、15.6±0.7、13.8±0.7、4.9±0.2、6.0±0.3 和 10.8±0.5µM）对 MCF7 的生长抑制活性最高。细胞周期分析表明，化合物 、 和 使细胞停滞在 G1 期，化合物 、 和 使细胞停滞在 S 期，化合物 使细胞停滞在 G1/S 期。化合物 、 、 、 、 和 的凋亡作用证实了它们具有早期和晚期凋亡作用。在 MCF10A 处理的正常细胞上，化合物 、 、 、 、 和 显示出良好的安全性特征。此外，化合物 、 和 显示出有希望的 CDK2 抑制活性（IC=0.22±0.01、0.25±0.01µM）。对接研究还表明，这些化合物与天然配体（5-溴靛红）具有类似的相互作用。ADMET 计算研究预测了靶向化合物有希望的药代动力学特征。
