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

Wanqiong Huang, Chen Pan, Yongliang Huang, Tao Huang, Xiaonan Dong, Yunzhou Chen, Huatian Shi, Taichu Lau, Wailun Man*, Wenxiu Ni*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

1 Citation (Scopus)

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.
Original languageEnglish
Article number108153
JournalChinese Chemical Letters
Volume34
Issue number10
Early online date15 Jan 2023
DOIs
Publication statusPublished - Oct 2023

Scopus Subject Areas

  • Chemistry(all)

User-Defined Keywords

  • Apoptosis
  • Autophagy
  • Chemotherapy
  • Glutathione depletion
  • Osmium complex

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