哌嗪-查尔酮衍生物的合成及抗宫颈癌活性

Synthesis of piperazine-chalcone derivatives and anti-cervical cancer activity

以甘草查尔酮为先导化合物,采用药效团拼合原理,设计、合成系列新型查尔酮类衍生物,并通过1H-NMR、^(13)C-NMR和HR-MS进行表征确认其结构。选用人宫颈癌HeLa、SiHa、C33A、HeLa/DDP细胞、人宫颈正常H8细胞和人脐静脉内皮HUEVC细胞为体外模型,对目标化合物进行增殖抑制活性测试,并采用Elisa法、联合顺铂用药、Western Blot和分子对接技术,对化合物7h与VEGFR-2和P-gp靶点进行初步研究。结果表明,化合物7h的抗癌活性较显著且对正常细胞的毒性低,对VEGFR-2和P-gp靶点具有一定抑制作用,并能够与靶点周围的氨基酸残基形成氢键相互作用力。

A series of novel chalcone derivatives were designed and synthesized using the principle of pharmacophore collocation with glycyrrhiza chalcone as the lead compound,and their structures were confirmed by 1H-NMR,^(13)C-NMR and HR-MS characterization.Human cervical cancer HeLa,SiHa,C33A,HeLa/DDP cells,human cervical normal H8 cells and human umbilical vein endothelial HUEVC cells were selected as in vitro models to test the proliferation inhibitory activity of the target compounds.Preliminary studies of compound 7h with VEGFR-2 and P-gp targets were performed using Elisa assay,co-cisplatin dosing,Western Blot and molecular docking techniques.The results showed that compound 7h had significant anticancer activity and low toxicity to normal cells,inhibited VEGFR-2 and P-gp targets,and was able to form hydrogen bonding interaction force with amino acid residues around the targets.