(Salen)osmium(VI) nitrides catalyzed glutathione depletion in chemotherapy |
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| Affiliation: | 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;1. College of Science, Inner Mongolia Agricultural University, Hohhot 010018, China;2. College of Chemistry, State Key Laboratory of Elemento-Organic Chemistry, Nankai University, Tianjin 300071, China;1. Department of Laboratory Medicine, Dongguan Institute of Clinical Cancer Research, Affiliated Dongguan Hospital, Southern Medical University, Dongguan 523058, China;2. Dongguan Institute of Clinical Cancer Research, Dongguan Key Laboratory of Precision Diagnosis and Treatment for Tumors, Affiliated Dongguan Hospital, Southern Medical University, Dongguan 523058, China;3. Department of General Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China;4. Affiliated Foshan Maternity & Child Healthcare Hospital, Southern Medical University (Foshan Maternity & Child Healthcare Hospital), Foshan 528000, China;1. Key Laboratory of Light Conversion Materials and Technology of Shandong Academy of Sciences, Advanced Materials Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250353, China;2. College of Chemistry and Materials Science, Northwest University, Xi''an 710069, China;3. College of Chemistry, State Key Laboratory of Elemento-Organic Chemistry, Nankai University, Tianjin 300071, China;4. Institute of Materia Medica, Chinese Academy of Medical Sciences, Beijing 100050, China;5. Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, Department of Chemistry, Fudan University, Shanghai 200438, China;6. Department of Polymer Science and Engineering, University of Science and Technology of China, Hefei 230026, China;7. School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, China;8. Key Laboratory for Advanced Materials, Frontiers Science Center for Materiobiology and Dynamic Chemistry, School of Chemistry and Molecular Engineering, Institute of Fine Chemicals, East China University of Science and Technology, Shanghai 200237, China;9. College of Chemistry, Sichuan University, Chengdu 610065, China;10. Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China;1. Department of Chemistry and the MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China;2. Department of Chemistry, Taiyuan Normal University, Jinzhong 030619, China;3. Department of Electronic Science, Xiamen University, Xiamen 361005, China;1. Key Laboratory of Mesoscopic Chemistry of MOE, Jiangsu Key Laboratory of Advanced Organic Materials, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, China;2. Institut de Chimie de Strasbourg, UMR 7177, CNRS, Université de Strasbourg, Strasbourg Cedex 67008, France;1. College of Chemistry and Chemical Engineering, Yantai University, Yantai 264005, China;2. College of Chemistry and Chemical Engineering, Jishou University, Jishou 416000, China |
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| Abstract: | 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)(OH2)](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. |
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