Design, Synthesis and Anti-cervical Cancer Activity of Novel Pyrrolidine-chalcone Derivatives

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.