(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: Journal Publications and ReviewsRGC 21 - Publication in refereed journalpeer-review

4 Citations (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. © 2023 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.
Original languageEnglish
Article number108153
JournalChinese Chemical Letters
Volume34
Issue number10
Online published15 Jan 2023
DOIs
Publication statusPublished - Oct 2023

Research Keywords

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

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