武汉工程大学学报2025，Vol.47Issue(5)：480-486,7.DOI:10.19843/j.cnki.CN42-1779/TQ.202407029
基于1,4-二氢吡啶衍生物抑制P-糖蛋白并增敏抗癌效应的研究
Inhibiting P-glycoprotein and sensitizing cancer cells to cisplatin using novel 1,4-dihydropyridine derivatives
摘要
Abstract
Chemotherapy is one of the common methods for treating malignant tumors.However,the multidrug resistance significantly reduces the efficiency of chemotherapy and interferes with tumor treatment.P-glycoprotein(P-gp),a transporter protein of the ABC transporter family,confers multidrug resistance(MDR)to cancer cells.Inhibiting its activity has emerged as a promising strategy to overcome chemoresistance.1,4-dihydropyridine(DHP)compounds are known for their diverse pharmacological effects,including P-gp inhibition.In this study,a series of novel DHP derivatives(DHP-1 to DHP-6)was synthesized.Using verapamil,a classic P-gp inhibitor,as a reference,molecular interaction analyses revealed the potential binding sites and binding energies of these derivatives with P-gp.In cisplatin-resistant lung cancer A549/DDP cells,all DHPs(DHP-1 to DHP-6)inhibited P-gp-mediated efflux of rhodamine 123.Furthermore,co-administration of cisplatin with the DHP derivatives significantly sensitized the resistant cells to cisplatin.Notably,DHP-2 enhanced the antitumor activity of cisplatin,achieving an IC50 of 13.12 mmol/L against A549/DDP cells.The developed DHP derivatives exhibited good biocompatibility and potent P-gp inhibitory effects,effectively reversing cisplatin resistance.These findings suggest their promising potential as antitumor adjuvants.关键词
1,4-二氢吡啶/多药耐药性/P-糖蛋白抑制剂/抗癌活性Key words
1,4-dihydropyridine/multidrug resistance/inhibitors for P-glycoprotein/anticancer activity分类
化学化工引用本文复制引用
舒签汇,李文,梅田恬,宋蔚,王凯..基于1,4-二氢吡啶衍生物抑制P-糖蛋白并增敏抗癌效应的研究[J].武汉工程大学学报,2025,47(5):480-486,7.基金项目
小分子原料药精准制造湖北省重点实验室开放课题(KHLA01001) （KHLA01001）
