(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

doi:10.1016/j.cclet.2023.108153

(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

Department of Chemistry

Research output: Contribution to journal › Journal article › peer-review

2 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 [Os^VI(N)(L^H)(OH₂)](PF₆) (1, L^H = 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 language	English
Article number	108153
Journal	Chinese Chemical Letters
Volume	34
Issue number	10
Early online date	15 Jan 2023
DOIs	https://doi.org/10.1016/j.cclet.2023.108153
Publication status	Published - Oct 2023

Scopus Subject Areas

Chemistry(all)

User-Defined Keywords

Apoptosis
Autophagy
Chemotherapy
Glutathione depletion
Osmium complex

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.cclet.2023.108153

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@article{742c52d9b47043e1b8ddd139e617a407,

title = "(Salen)osmium(VI) nitrides catalyzed glutathione depletion in chemotherapy",

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.",

keywords = "Apoptosis, Autophagy, Chemotherapy, Glutathione depletion, Osmium complex",

author = "Wanqiong Huang and Chen Pan and Yongliang Huang and Tao Huang and Xiaonan Dong and Yunzhou Chen and Huatian Shi and Taichu Lau and Wailun Man and Wenxiu Ni",

note = "Publisher copyright: {\textcopyright} 2023 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. Funding Information: This work was 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), and Research Grants Council of Hong Kong (No. HKBU 12300121). W.L. Man thanks Hong Kong Baptist University for the start-up fund (No. RC-OFSGT2/20-21/SCI/008). This work is also supported by {"}Laboratory for Synthetic Chemistry and Chemical Biology{"} under the Health@InnoHK Program launched by Innovation and Technology Commission, The Government of Hong Kong Special Administrative Region of the People's Republic of China.",

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doi = "10.1016/j.cclet.2023.108153",

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TY - JOUR

T1 - (Salen)osmium(VI) nitrides catalyzed glutathione depletion in chemotherapy

AU - Huang, Wanqiong

AU - Pan, Chen

AU - Huang, Yongliang

AU - Huang, Tao

AU - Dong, Xiaonan

AU - Chen, Yunzhou

AU - Shi, Huatian

AU - Lau, Taichu

AU - Man, Wailun

AU - Ni, Wenxiu

N1 - Publisher copyright: © 2023 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. Funding Information: This work was 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), and Research Grants Council of Hong Kong (No. HKBU 12300121). W.L. Man thanks Hong Kong Baptist University for the start-up fund (No. RC-OFSGT2/20-21/SCI/008). This work is also supported by "Laboratory for Synthetic Chemistry and Chemical Biology" under the Health@InnoHK Program launched by Innovation and Technology Commission, The Government of Hong Kong Special Administrative Region of the People's Republic of China.

PY - 2023/10

Y1 - 2023/10

N2 - 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.

AB - 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.

KW - Apoptosis

KW - Autophagy

KW - Chemotherapy

KW - Glutathione depletion

KW - Osmium complex

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DO - 10.1016/j.cclet.2023.108153

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ER -

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

Abstract

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