新型哌啶-查尔酮类衍生物的设计、合成及抗宫颈癌和逆转顺铂耐药活性

Design, Synthesis, Anti-Cervical Cancer and Reversal of CisplatinResistance Activity of Novel Piperidine-Chalcone Derivatives

本文采用活性亚结构拼接原理,设计并合成了15个新型含哌啶的查尔酮类衍生物,利用~1H NMR、~(13)C NMR和HR-MS对结构进行表征,并初步评价了其抗宫颈癌和抗顺铂耐药宫颈癌活性作用。结果表明,化合物6g具有一定的抗肿瘤活性和逆转顺铂耐药作用;并采用Elisa法、联合顺铂用药、Western Blot和分子对接对化合物6g与VEGFR-2和P-gp靶点进行了初步的研究。本研究为基于VEGFR-2和P-gp双靶点新型分子靶向查尔酮类衍生物的设计提供了一条思路。

In this paper,15 novel piperidine-containing chalcone derivatives were designed and synthesized using the active substructure splicing principle,and their structures were characterized by'H NMR,3C NMR and HR-MS.Their active effects of anti-cervical cancer and anti-cisplatin-resistant cervical cancer were preliminarily evaluated.The results showed that compound 6g has some antitumor activity and reversal effect on cisplatin resistance.The preliminary studies of compound 6g with VEGFR-2 and P-gp targets were performed using Elisa assay,co-dosing with cisplatin,Western Blot and molecular docking.This study provides an idea for the design of novel molecularly targeted chalcone derivatives based on the dual targets of VEGFR-2 and P-gp.