(Salen)osmium (Ⅵ) nitrides catalyzed glutathione depletion in chemotherapy  

作　　者：Wanqiong Huang Chen Pan Yongliang Huang Tao Huang Xiaonan Dong Yunzhou Chen Huatian Shi Taichu Lau Wailun Man Wenxiu Ni 

机构地区：[1]Department of Medicinal Chemistry,Shantou University Medical College,Shantou 515041,China [2]Department of Chemistry,Hong Kong Baptist University,Hong Kong,China [3]Department of Chemistry,City University of Hong Kong,Hong Kong,China [4]Chemistry and Chemical Engineering Guangdong Laboratory,Shantou 515063,China

出　　处：《Chinese Chemical Letters》2023年第10期185-190,共6页中国化学快报（英文版）

基　　金：financially supported by the Guangdong Major Project of Basic and Applied Basic Research(No.2019B030302009);the National Natural Science Foundation of China(No.21401125);the Li Ka Shing Foundation Cross-Disciplinary Research Grant(No.2020LKSFG01F);Research Grants Council of Hong Kong(No.HKBU 12300121);Hong Kong Baptist University for the start-up fund(No.RC-OFSGT2/20-21/SCI/008);supported by"Laboratory for Synthetic Chemistry and Chemical Biology"under the Health@Inno HK Program launched by Innovation and Technology Commission,The Government of Hong Kong Special Administrative Region of the People’s Republic of China。

摘　　要：Glutathione depletion provides a promising strategy for the design of non-platinum anticancer drugs.Here we report a series of electrophilic (salen)osmium(Ⅵ) nitrides that react with glutathione to generate (salen)osmium(Ⅲ) ammine compounds.In vitro studies indicate that these osmium(VI) nitrides show comparable cytotoxicity to cisplatin against various carcinoma.Mechanistic studies with the representative compound[OsⅥ(N)(LH)(OH_(2))](PF6)(1,LH=N,N’-bis(salicylidene)-o-cyclohexyldiamine dianion) suggest that 1 induces glutathione depletion,reactive oxygen species generation,endoplasmic reticulum stress,and in turn triggers death receptor-mediated apoptosis and autophagy in lung cancer cells.In vivo evaluations show that 1 can inhibit tumor xenograft growth effectively with no body weight drop.

关 键 词：CHEMOTHERAPY Osmium complex Glutathione depletion APOPTOSIS AUTOPHAGY 

分 类 号：R313[医药卫生—基础医学] TQ460.1[化学工程—制药化工]