设计和合成新的螺环氧吲哚候选物及其硒纳米颗粒作为潜在的双重拓扑异构酶I/II抑制剂、DNA插入剂和诱导凋亡剂。
Design and synthesis of new spirooxindole candidates and their selenium nanoparticles as potential dual Topo I/II inhibitors, DNA intercalators, and apoptotic inducers.
发表日期：2023 Aug 17
作者：
Samar El-Kalyoubi, Mohamed M Khalifa, Mahmoud T Abo-Elfadl, Ahmed A El-Sayed, Ahmed Elkamhawy, Kyeong Lee, Ahmed A Al-Karmalawy
来源：
J Enzym Inhib Med Ch
摘要：
通过拼接螺环内酮类化合物和嘧啶类化合物，设计并合成了一系列新颖的双重拓扑异构酶I/II抑制剂。对某些衍生物合成了原位硒纳米颗粒（SeNPs）。评估了目标物和SeNP衍生物对五种癌细胞系的细胞毒性。此外，还测定了最佳成员对拓扑异构酶I和拓扑异构酶II的抑制能力和DNA夹入能力。化合物7d NPs表现出最佳的对拓扑异构酶I和拓扑异构酶II的抑制活性，IC50分别为0.042和1.172μM。研究了化合物7d NPs对细胞周期和诱导凋亡的作用。在A549细胞中，该化合物使细胞周期停滞在S期，并使凋亡率从23.81%（对照组）增加到41.02%。随后进行了体外研究，以研究设计的成员与靶蛋白的可能结合作用。
A new wave of dual Topo I/II inhibitors was designed and synthesised via the hybridisation of spirooxindoles and pyrimidines. In situ selenium nanoparticles (SeNPs) for some derivatives were synthesised. The targets and the SeNP derivatives were examined for their cytotoxicity towards five cancer cell lines. The inhibitory potencies of the best members against Topo I and Topo II were also assayed besides their DNA intercalation abilities. Compound 7d NPs exhibited the best inhibition against Topo I and Topo II enzymes with IC50 of 0.042 and 1.172 μM, respectively. The ability of compound 7d NPs to arrest the cell cycle and induce apoptosis was investigated. It arrested the cell cycle in the A549 cell at the S phase and prompted apoptosis by 41.02% vs. 23.81% in the control. In silico studies were then performed to study the possible binding interactions between the designed members and the target proteins.