(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 › Article › peer-review

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
Journal	Chinese Chemical Letters
DOIs	https://doi.org/10.1016/j.cclet.2023.108153
Publication status	Accepted/In press - 15 Jan 2023

User-Defined Keywords

Chemotherapy
Osmium complex
Glutathione depletion
Apoptosis
Autophagy

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10.1016/j.cclet.2023.108153

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

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.",

year = "2023",

month = jan,

day = "15",

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

language = "English",

journal = "Chinese Chemical Letters",

issn = "1001-8417",

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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

PY - 2023/1/15

Y1 - 2023/1/15

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 - Chemotherapy

KW - Osmium complex

KW - Glutathione depletion

KW - Apoptosis

KW - Autophagy

U2 - 10.1016/j.cclet.2023.108153

DO - 10.1016/j.cclet.2023.108153

M3 - Article

SN - 1001-8417

JO - Chinese Chemical Letters

JF - Chinese Chemical Letters

ER -

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

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