OBJECTIVE To design and synthesize of a series of novel azachalcone derivatives and study of their anti-cervical cancer activity and mechanism of action.METHODS A series of novel chalcone derivatives were designed and synthesized by using glycyrrhiza chalcone as the lead compound and VEGFR-2 and P-gp as the target sites using the active substructure splicing principle,and the structures were characterized by 1H-NMR,13C-NMR and HR-MS.MTT,ELISA,co-dosing with cisplatin,Western blotting and molecular docking assays were used to preliminarily evaluate the proliferation inhibitory activity and mechanism of action of the target compounds on cervical cancer and cisplatin-resistant cervical cancer cells.RESULTS Compound 7h showed some antitumor activity and reversal of cisplatin resistance,and had some inhibitory effects on phosphorylation of VEGFR-2 and downstream PI3K/AKT signaling pathway proteins,with no significant differences on P-gp protein expression compared with the blank group in the concentration range of 0.5,1.0,1.5 μmol·L-1.CONCLUSION The anti-cervical cancer activity and reversal of cisplatin resistance of compound 7h may be related to its inhibition of VEGFR-2 and P-gp targets.
关键词
先导化合物/查尔酮类衍生物/宫颈癌/顺铂耐药宫颈癌/新型分子靶向
Key words
lead compound/chalcone derivatives/cervical cancer/cisplatin-resistant cervical cancer/novel molecular targeting
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