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Topoisomerase I Inhibition, DNA Photocleavage Activity, and G-Quadruplex DNA ‘Light Switch’ Based on Nitro-Substituted Ruthenium Complexes

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Abstract

Two ruthenium complexes containing nitro-substituted ligand, [Ru(bpy)2(hnpip)](PF6)2 (1) and [Ru(phen)2(hnpip)](PF6)2 (2) (bpy = 2,2'-bipyridine; phen = 1,10-phenanthroline; hnpip = 2-(3-hydroxyl- 4-nitrophenyl)imidazo[4,5-f][1,10-phenanthroline] were synthesized and characterized. DNA binding behaviors were studied by luminescent titration, UV-vis titration, FRET (FRET = Fluorescence resonance energy transfer) and molecular docking experiments. Complex 2 exhibited “light switch” effect upon addition of G-quadruplex DNA and displayed fluorescent selectivity towards G-quadruplex DNA over other DNAs in the presence of K4[Fe(CN)6]. Fluorescence experiments, FRET experiments and molecular docking results indicated that the selectivity may be attributed to protection of nitro group from water, DNA affinity and the difference in DNA structures. Furthermore, both complexes were found to cleave DNA under irradiation by the formation of singlet oxygen. DNA topoisomerase inhibition experiments indicated that complex 2 exhibited higher topoisomerase I inhibition activity (IC50 = 18 μM) than complex 1 (IC50 = 50 μM). Docking studies revealed that complex 2 stabilized Top1cc complex via π–π interaction and the formation of hydrogen bond.

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Funding

This work was supported by the Research Foundation of Education Bureau of Hunan Province (16A145) and State Key Laboratory of Coordination Chemistry (SKLCC1920).

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Authors and Affiliations

  1. Hunan Province Cooperative Innovation Center for the Construction and Development of Dongting Lake Ecological Economic Zone, Hunan Provincial Key Laboratory of Water Treatment Functional Materials, Hunan Province Engineering Research Center of Electroplating Wastewater Reuse Technology, College of Chemistry and Materials Engineering, Hunan University of Arts and Science, 415000, Changde, China

    Xue-Wen Liu, Ning-Yi Liu, Yuan-Qing Deng, Shan Wang & Ting Liu

  2. State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, 210023, Nanjing, China

    Xue-Wen Liu

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Xue-Wen Liu, Liu, NY., Deng, YQ. et al. Topoisomerase I Inhibition, DNA Photocleavage Activity, and G-Quadruplex DNA ‘Light Switch’ Based on Nitro-Substituted Ruthenium Complexes. Russ. J. Inorg. Chem. 65, 1186–1195 (2020). https://doi.org/10.1134/S0036023620080094

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