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Facile induction and stabilization of intramolecular antiparallel G-quadruplex of d(TTAGGG)n on interaction with triazine-2-imidazole ethyl amine compound and its Cu(II), Zn(II) complexes under no-salt conditions

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Abstract

The compounds trizImEA, Cu-trizImEA and Zn-trizImEA were synthesized and characterized by CHN, IR, NMR and mass measurements. They were interacted with CT DNA, and human telomere DNA, HTelo8 and HTelo20 to elucidate their binding capacity with different DNA structures. The interactions were followed by circular dichrosim (CD) measurements, fluorescent intercalator displacement (FID) assays and molecular docking studies through MOE program. The CD studies reveal the G-quadruplex stabilization of both HTelo8 and HTelo20 under salt conditions by the pure ligand, Cu-trizImEA and Zn-trizImEA. The compounds also induce and stabilize, selectively antiparallel G-quadruplex conformation on d(TTAGGG)n under no salt conditions. The binding constant (Kb) values calculated for the ligand and complexes are in the range of 5.3 × 104 M−1 to 9.4 × 105 M−1 revealing the strong binding. The FID assays clearly indicate the strong binding of the compounds on the G-quadruplex structure, as they displace thiazole orange (TO) which was bound to G-quadruplex already through specific intercalation. Molecular docking studies revealed classical intercalation as the preferred mode of interaction for all the three compounds in case of the stabilization towards antiparallel conformation. The compound's ability on antitelomerase activity and anticancer activities were performed and was found to be very effective in various cancer cell lines. The IC50 values observed were in the range of 50–100 nM for anticancer activity. Thus the compounds can be considered as effective anticancer agents as they stabilize G-quadruplex structures in a more facile and effective way towards antitelomerase action.

Graphical abstract

The pure ligand, Cu-trizImEA and Zn-trizImEA compounds were induce and stabilize, selectively antiparallel G-quadruplex conformation on d(TTAGGG)n under no salt conditions. The formed G-quadruplexes were thermodynamically stable and irreversible, thus resulting in proficient antitelomerase and anticancer activity, in-vitro.

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Acknowledgements

Prof. Raghavan, MBU, IISc., Bangalore is thanked for CD facility. DST-WOS-A (SR/WOS-A/CS-75/2016), India is acknowledged for financial support.

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Authors and Affiliations

  1. Department of Chemistry, Selvamm Arts and Science College, Namakkal, 637003, Tamilnadu, India

    Renuga Duraisamy

  2. Department of Chemical Engineering, National Institute of Technology, Tiruchirappalli, 620015, Tamilnadu, India

    Uma Maheswari Palanisamy & K M Meera Sheriffa Begum

  3. National Facility for Marine Cyanobacteria, Department of Marine Biotechnology, Bharathidasan University, Tiruchirappalli, 620024, Tamilnadu, India

    Prabaharan Dharmar

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  1. Renuga Duraisamy
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Duraisamy, R., Palanisamy, U., Sheriffa Begum, K.M.M. et al. Facile induction and stabilization of intramolecular antiparallel G-quadruplex of d(TTAGGG)n on interaction with triazine-2-imidazole ethyl amine compound and its Cu(II), Zn(II) complexes under no-salt conditions. J Chem Sci 134, 12 (2022). https://doi.org/10.1007/s12039-021-01996-1

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  • DOI: https://doi.org/10.1007/s12039-021-01996-1

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