典型文献
Dual Diomarkers Triggered Prodrugs for Precise Treatment of Melanoma:Design,Synthesis and Activities
文献摘要：
Targeted prodrug strategy,which utilizes the endogenous biomarkers in cancer cells as activators to release the active drug,has been well established either in the fundamental research or the clinical treatment.However,many prodrugs suffer from safety concern due to"off-target activation".Dual or multiple biomarkers triggered prodrug may provide an effective strategy to overcoming the"off-target effect".Melanoma cells have both high levels of reactive oxygen species(ROS)and tyrosinase(TYR),which makes them significantly different from other tumor cells and normal cells.Here we reported a series of quinazolinone-aryl boronic acid/ester-based prodrugs,which can be activated by the cascade of ROS and TYR and selectively kill melanoma cells.The structure-activity relationship(SAR)analysis revealed that mitochondria-targeting property was vital for their cytotoxicity and the dual activated effector played a significant role in their selectivity towards melanoma cells.Among these candidates,compound 4b showed the highest toxicity to B16,leading to an imbalance of the redox system in melanoma cells,causing mitochondrial DNA damage,and then promoting melanoma cells death.
文献关键词：
中图分类号：
作者姓名：
RUAN Yawen;HUANG Peiling;YAN Jiangyu;LI Guorui;HUANG JingI
作者机构：
State Key Laboratory of Chemo/Biosensing and Chemometrics,School of Biomedical Sciences,Hunan University,Changsha 410082,P.R.China
文献出处：
引用格式：
[1]RUAN Yawen;HUANG Peiling;YAN Jiangyu;LI Guorui;HUANG JingI-.Dual Diomarkers Triggered Prodrugs for Precise Treatment of Melanoma:Design,Synthesis and Activities)[J].高等学校化学研究（英文版）,2022(04):949-956
A类：
Diomarkers,Prodrugs,quinazolinone
B类：
Dual,Triggered,Precise,Treatment,Melanoma,Design,Synthesis,Activities,Targeted,strategy,which,utilizes,endogenous,biomarkers,cancer,cells,activators,release,has,been,well,established,either,fundamental,research,clinical,treatment,However,many,prodrugs,suffer,from,safety,concern,due,off,activation,multiple,triggered,may,provide,effective,overcoming,have,both,levels,reactive,oxygen,species,ROS,tyrosinase,TYR,makes,them,significantly,different,other,tumor,normal,Here,reported,series,aryl,boronic,acid,ester,activated,by,cascade,selectively,kill,melanoma,structure,activity,relationship,SAR,analysis,revealed,that,targeting,property,was,vital,their,cytotoxicity,dual,effector,played,role,selectivity,towards,Among,these,candidates,compound,4b,showed,highest,B16,leading,imbalance,redox,system,causing,mitochondrial,damage,then,promoting,death
AB值：
0.63908
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机标中图分类号，由域田数据科技根据网络公开资料自动分析生成，仅供学习研究参考。
