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Novel iridium(III) iminopyridine complexes: synthetic, catalytic, and in vitro anticancer activity studies

  • Deliang Kong
  • Meng Tian
  • Lihua Guo
  • Xicheng Liu
  • Shumiao Zhang
  • Yameng Song
  • Xin Meng
  • Shu Wu
  • Lingzi Zhang
  • Zhe Liu
Original Paper
  • 10 Downloads

Abstract

Organometallic half-sandwich IrIII complexes of the type [(η5-Cpx)Ir(N^N)Cl]PF6 16, where Cpx = C5Me5 (Cp*), C5Me4C6H5 (Cpxph), C5Me4C6H4C6H5 (Cpxbiph), N^N is imionopyridine chelating ligand, were prepared and characterized. The X-ray crystal structure of complex 1 has been determined. Four compounds displayed higher anticancer potency than clinically used anticancer drug cisplatin against A549 cancer cells, especially complex 3 which is 8 times more active than cisplatin. No hydrolysis was observed by NMR and UV–Vis for complexes 3 and 6; however, these complexes show big differences in nucleobase binding, mainly decided by the imionopyridine chelating ligand. Complex 3 is stable in the presence of glutathione, but 6 reacted rapidly with glutathione. The octanol/water partition coefficients (log P) of 3 and 6 have been determined. In addition, these complexes display effective catalytic activity in converting coenzyme NADH to NAD+ by accepting hydride to form an Ir hydride adduct. The mechanism of actions of these complexes involves apoptosis induction, cell cycles arrest, and significant increase of reactive oxygen species levels in A549 cancer cells.

Keywords

Iridium Anticancer drug 

Notes

Acknowledgements

We thank the National Natural Science Foundation of China (Grant no. 21671118) and the Taishan Scholars Program for support.

Supplementary material

775_2018_1578_MOESM1_ESM.pdf (1.3 mb)
Supplementary material 1 (PDF 1349 kb)

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Copyright information

© SBIC 2018

Authors and Affiliations

  1. 1.Department of Chemistry and Chemical Engineering, Institute of Anticancer Agents Development and Theranostic Application, The Key Laboratory of Life-Organic Analysis and Key Laboratory of Pharmaceutical Intermediates and Analysis of Natural MedicineQufu Normal UniversityQufuChina

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