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

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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 1–3 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.

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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).

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Authors and Affiliations

  1. School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510006, People’s Republic of China

    Qiao-Yan Yi, Wen-Yao Zhang, Miao He, Fan Du, Xiu-Zhen Wang, Yang-Jie Wang, Yi-Ying Gu, Lan Bai & Yun-Jun Liu

  2. Guangdong Engineering Research Center for Lead Compounds and Drug Discovery, Guangzhou, 510006, People’s Republic of China

    Yun-Jun Liu

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  1. Qiao-Yan Yi
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Correspondence to Xiu-Zhen Wang or Yun-Jun Liu.

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Yi, QY., Zhang, WY., He, M. et al. Anticancer and antibacterial activity in vitro evaluation of iridium(III) polypyridyl complexes. J Biol Inorg Chem 24, 151–169 (2019). https://doi.org/10.1007/s00775-018-1635-8

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  • DOI: https://doi.org/10.1007/s00775-018-1635-8

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