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Anticancer and antibacterial activity in vitro evaluation of iridium(III) polypyridyl complexes

  • Qiao-Yan Yi
  • Wen-Yao Zhang
  • Miao He
  • Fan Du
  • Xiu-Zhen Wang
  • Yang-Jie Wang
  • Yi-Ying Gu
  • Lan Bai
  • Yun-Jun Liu
Original Paper
  • 120 Downloads

Abstract

Three iridium(III) polypyridyl complexes [Ir(ppy)2(PYTA)](PF6) (1) (ppy = 2-phenylpyridine), [Ir(bzq)2(PYTA)](PF6) (2) (bzq = benzo[h]quinolone) and [Ir(piq)2(PYTA)](PF6) (3) (piq = 1-phenylisoquinoline, PYTA = 2,4-diamino-6-(2′-pyridyl)-1,3,5-triazine) were synthesized and characterized by elemental analysis, IR, 1H NMR and 13C NMR. The cytotoxic activity of the complexes toward cancer SGC-7901, Eca-109, A549, HeLa, HepG2, BEL-7402 and normal LO2 cell lines was investigated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. Complex 3 shows the most effective on inhibiting the above cell growth among these complexes. The complexes locate at the lysosomes and mitochondria. AO/EB, Annex V and PI and comet assays indicate that the complexes can induce apoptosis in SGC-7901 cells. Intracellular ROS and mitochondrial membrane potential were examined under fluorescence microscopy. The results demonstrate that the complexes increase the intracellular ROS levels and induce a decrease in the mitochondrial membrane potential. The complexes can enhance intracellular Ca2+ concentration and cause a release of cytochrome c. The autophagy was studied using MDC staining and western blot. Complexes 13 can effectively inhibit the cell invasion with a concentration-dependent manner. Additionally, the complexes target tubules and inhibit the polymerization of tubules. The antimicrobial activity of the complexes against S. aureus, E. coli, Salmonella and L. monocytogenes was explored. The mechanism shows that the complexes induce apoptosis in SGC-7901 cells through ROS-mediated lysosomal–mitochondrial, targeting tubules and damage DNA pathways.

Graphical Abstract

Three iridium(III) complexes [Ir(N–C)2(PYTA)](PF6) (N–C = ppy, 1; bzq, 2; piq, 3) were synthesized and characterized. The anticancer activity of the complexes against SGC-7901 cells was studied by apoptosis, comet assay, autophagy, ROS, mitochondrial membrane potential, intracellular Ca2+ levels, release of cytochrome c, tubules and western blot analysis. The antibacterial activity in vitro was also assayed.

Keywords

Iridium(III) complexes Apoptosis Cell cycle distribution Antibacterial activity Western blot 

Notes

Acknowledgements

This work was supported by the National Nature Science Foundation of China (No 21877018) and the Natural Science Foundation of Guangdong Province (No 2016A030313728).

Supplementary material

775_2018_1635_MOESM1_ESM.pdf (459 kb)
Supplementary material 1 (PDF 458 kb)

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Copyright information

© Society for Biological Inorganic Chemistry (SBIC) 2018

Authors and Affiliations

  • Qiao-Yan Yi
    • 1
  • Wen-Yao Zhang
    • 1
  • Miao He
    • 1
  • Fan Du
    • 1
  • Xiu-Zhen Wang
    • 1
  • Yang-Jie Wang
    • 1
  • Yi-Ying Gu
    • 1
  • Lan Bai
    • 1
  • Yun-Jun Liu
    • 1
    • 2
  1. 1.School of PharmacyGuangdong Pharmaceutical UniversityGuangzhouPeople’s Republic of China
  2. 2.Guangdong Engineering Research Center for Lead Compounds and Drug DiscoveryGuangzhouPeople’s Republic of China

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