比卡鲁胺配位铂的合成及抗肿瘤活性  

Synthesis and antitumor activity of bicalutamide-platinum complex

作　　者：陈育婷 王浩冰 张平玉 CHEN Yuting;WANG Haobing;ZHANG Pingyu(College of Chemistry and Environmental Engineering,Shenzhen University,Shenzhen 518071,Guangdong Province,P.R.China)

机构地区：[1]深圳大学化学与环境工程学院,广东深圳518071

出　　处：《深圳大学学报（理工版）》2024年第4期463-470,共8页Journal of Shenzhen University(Science and Engineering)

基　　金：国家自然科学基金资助项目(22077085);广东省自然科学基金资助项目(2023B1515020060)。

摘　　要：铂类药物是一类在临床上应用广泛的抗癌药物,其毒副作用和耐药性仍是亟待解决的难题.为提高铂类药物的药效和抵抗单一药物的耐药性,将铂配合物与临床抗肿瘤药物比卡鲁胺配位偶联,成功制备了一种能够进行肿瘤光动力治疗的新型铂类配合物(platinum-bicalutamide,Pt-BIC),通过核磁共振和质谱表征目标配合物;采用9,10-蒽二基-双(亚甲基)二丙二酸单线态氧探针检测发现,在550 nm的光照条件下Pt-BIC能够产生强氧化性的单线态氧(^(1)O_(2)),进而氧化细胞内的还原型辅酶I(nicotinamide adenine dinucleotide reduced coenzyme I,NADH),破坏NADH和烟酰胺腺嘌呤二核苷酸/辅酶I(nicotinamide adenine dinucleotide,NAD^(+))的氧化还原平衡状态;采用噻唑蓝比色法测定Pt-BIC对肿瘤细胞的光毒性,结果表明,Pt-BIC的抗肿瘤活性优于单一顺铂和单一比卡鲁胺;采用2′,7′-二氯荧光素二乙酸酯(2′,7′-dichlorofluorescin diacetate,DCFH-DA)探针检测发现,Pt-BIC在550 nm光照条件下能够促进细胞内活性氧的产生.研究工作不仅为新型铂类药物的设计和开发提供了新策略,也为癌症治疗带来新希望.Platinum-based compounds are important anticancer drugs owing to their widespread clinical use and remarkable therapeutic efficacy.However,their side effects and drug resistance remain pressing clinical challenges.In order to improve drug efficacy and overcome drug resistance,we successfully prepared a novel platinum complex(platinum-bicalutamide,Pt-BIC)for photodynamic therapy of tumors by coupling platinum with clinical anti-tumor drug bicalutamide.The target complex was characterized by nuclear magnetic resonance and mass spectrometry.Using the 9,10-anthracenediyl-bis(methylene)dimalonic acid(ABDA)singlet oxygen probe,we detected that Pt-BIC was found to generate singlet oxygen(^(1)O_(2))under 550 nm light irradiation,which subsequently oxidizes the intracellular reduced coenzyme I(NADH),disrupting the NADH-nicotinamide adenine dinucleotide(NAD^(+))banlance.Additionally,the phototoxicity of Pt-BIC on tumor cells was measured using 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide(MTT)method,and the results showed that the anti-tumor activity of Pt-BIC was superior to that of cisplatin and bicalutamide.Pt-BIC can promote the production of intracellular reactive oxygen species using 2′,7′-dichlorofluorescin diacetate(DCFH-DA)probe under 550 nm light irradiation.This study not only provides a new strategy for the design and development of novel platinum-based drugs, but also holds promise for advancing cancer therapy.

关 键 词：生物化学 光动力治疗 抗肿瘤药物 铂配合物 比卡鲁胺 还原型辅酶I 

分 类 号：Q819[生物学—生物工程]