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Dalton Transactions
Page 5 of 7
DOI: 10.1039/C8DT03159B
Journal Name
ARTICLE
10.
11.
T. C. Johnstone, K. Suntharalingam and S. J. Lippard,
Chem. Rev., 2016, 116, 3436-3486.
S. K. Fung, T. Zou, B. Cao, P.-Y. Lee, Y. M. E. Fung, D. Hu,
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Chao, Dalton Trans., 2016, 45, 13135-13145.
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S. Thota, D. A. Rodrigues, D. C. Crans and E. J. Barreiro, J.
Med. Chem., 2018, 61, 5805-5821.
S. Thota and D. Crans, Introduction: Synthesis and
Applications in Pharmaceutical Sciences, 2017.
Y. Yang, G. Lihua, Z. Tian, X. Liu, Y. Gong, H. Zheng, X. Ge
and Z. Liu, Chem. Asian J., 2018, DOI:
Conclusions
The development of metal-NHCs in medicinal and biological
chemistry is very rapid. In this paper, we designed twelve phenoxide
chelated IrIII-NHC complexes and studied their anticancer activity.
Complexes 1-12 showed activity towards A549 cells and HeLa
cells, especially these complexes had even higher inhibitory effect
than cisplatin. Altering the complexes' structure may influence their
anticancer activity. The tested complexes hydrolyzed in aqueous
solution. However, these complexes displayed no bounding to 9-
MeA and 9-EtG and no cleavage to pBR322 DNA. They showed a
little binding affinity to CT-DNA, probably through non-covalent
binding modes. Thus, DNA may not be the primary target of these
complexes. Complexes interfere with NADH/NAD+ hydrogen transfer,
which produce the ROS. ROS level detection increased in the cells
after addition complexes 6 and 12. Complex 2 and 12 influenced the
cell cycle at the G0/G1 phase. Apoptotic cells and mitochondrial
dysfunction were observed, which may be contributed to anticancer
activity. Complex 6 cause lysosomal damage through confocal
microscopy observation. The findings demonstrated that half-
sandwich IrIII-NHC complexes converted NADH to NAD+, which
produced the ROS. ROS level detection confirmed that ROS levels
12.
13.
14.
15.
16.
17.
18.
10.1002/asia.201801058.
Q. Du, L. Guo, M. Tian, X. Ge, Y. Yang, X. Jian, Z. Xu, Z. Tian
and Z. Liu, Organometallics, 2018, DOI:
did increase. The production of ROS led to
a decrease in
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22.
mitochondrial membrane potential and lysosomal damage, and
finally induced apoptosis.
10.1021/acs.organomet.8b00402.
All the results appear that phenoxide chelated IrIII-NHC complexes
[(η5-Cpx)Ir(C^O)Cl] have well anti-cancer effects. It is hoped that
these type complexes will continue to be studied and become
effective human anti-cancer drugs.
Z. Xu, D. Kong, X. He, L. Guo, X. Ge, X. Liu, H. Zhang, J. Li, Y.
Yang and Z. Liu, Inorg. Chem. Front., 2018, DOI:
10.1039/C8QI00476E.
Z. Tian, J. Li, S. Zhang, Z. Xu, Y. Yang, D. Kong, H. Zhang, X.
Ge, J. Zhang and Z. Liu, Inorg. Chem., 2018, DOI:
10.1021/acs.inorgchem.8b01944.
E. Z. Jahromi, A. Divsalar, A. A. Saboury, S. Khaleghizadeh,
H. Mansouri-Torshizi and I. Kostova, J. Iran. Chem. Soc.,
2016, 13, 967-989.
Conflicts of interest
There are no conflicts to declare.
23.
24.
T. Zou, C.-N. Lok, P.-K. Wan, Z.-F. Zhang, S.-K. Fung and C.-
M. Che, Curr. Opin. Chem. Biol., 2018, 43, 30-36.
M. Z. Ghdhayeb, R. A. Haque, S. Budagumpi, M. B.
Khadeer Ahamed and A. M. S. A. Majid, Inorg. Chem.
Commun., 2017, 75, 41-45.
R. J. Needham, C. Sanchez-Cano, X. Zhang, I. Romero-
Canelón, A. Habtemariam, M. S. Cooper, L. Meszaros, G. J.
Clarkson, P. J. Blower and P. J. Sadler, Angew. Chem. Int.
Ed., 2017, 56, 1017-1020.
Acknowledgements
We thank the National Natural Science Foundation of China
(21671118), the Taishan Scholars Program and Shandong
Provincial Natural Science Foundation (ZR2018LB007) for
support.
25.
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C. Sanchez-Cano, I. Romero-Canelón, Y. Yang, I. J. Hands-
Portman, S. Bohic, P. Cloetens and P. J. Sadler, Chem. Eur.
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J. M. Hearn, I. Romero-Canelón, B. Qamar, Z. Liu, I. Hands-
Portman and P. J. Sadler, ACS Chem. Biol., 2013, 8, 1335-
1343.
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This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 5
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