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 - 2023/10
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. © 2023 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.
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. © 2023 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.
KW - Apoptosis
KW - Autophagy
KW - Chemotherapy
KW - Glutathione depletion
KW - Osmium complex
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UR - https://www.scopus.com/record/pubmetrics.uri?eid=2-s2.0-85165241568&origin=recordpage
U2 - 10.1016/j.cclet.2023.108153
DO - 10.1016/j.cclet.2023.108153
M3 - RGC 21 - Publication in refereed journal
SN - 1001-8417
VL - 34
JO - Chinese Chemical Letters
JF - Chinese Chemical Letters
IS - 10
M1 - 108153
ER -