首页|新型吡咯烷-查尔酮类衍生物的设计、合成及抗宫颈癌活性研究

新型吡咯烷-查尔酮类衍生物的设计、合成及抗宫颈癌活性研究

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目的 设计、合成系列新型氮杂查尔酮类衍生物并研究其抗宫颈癌活性和作用机制。方法 以甘草查尔酮为先导化合物，以VEGFR-2和P-gp为靶点，采用活性亚结构拼接原理，设计并合成一系列新型查尔酮类衍生物，利用1H-NMR、13C-NMR和HR-MS对结构进行表征。采用MTT、ELISA、联合顺铂用药、Western blotting和分子对接试验，初步评价了目标化合物对宫颈癌和顺铂耐药宫颈癌细胞的增殖抑制活性及作用机制。结果 化合物7h具有一定的抗肿瘤活性和逆转顺铂耐药作用，对VEGFR-2及下游PI3K/AKT信号通路蛋白的磷酸化具有一定的抑制作用，并在0。5，1。0，1。5 μmol·L-1浓度内对P-gp蛋白表达量与空白组相比无显著性差异。结论 化合物7h的抗宫颈癌活性和逆转顺铂耐药作用，可能与其抑制了 VEGFR-2和P-gp靶点有关。
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.

lead compoundchalcone derivativescervical cancercisplatin-resistant cervical cancernovel molecular targeting

杨争、刘正叶、木合布力·阿布力孜、艾孜提艾力·艾海提、玉苏普瓦吉木·阿力木江、廖波儿、赛力克阿拉·阿里汗

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新疆医科大学药学院,乌鲁木齐 830011

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

国家自然科学基金国家自然科学基金新疆维吾尔自治区重点实验室项目新疆维吾尔自治区科技计划新疆教育厅研究生科研创新项目

8216065481960625XJDX17132022D01C210XJ2022G168

2024

10.13748/j.cnki.issn1007-7693.20230818

中国现代应用药学
中国药学会

中国现代应用药学

CSTPCD北大核心
影响因子：0.877
ISSN：1007-7693
年,卷(期)：2024.41(4)
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