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

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, HTelo 8 and HTelo 20 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 HTelo 8 and HTelo 20 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 ( K b ) values calculated for the ligand and complexes are in the range of 5.3 × 10 4 M −1 to 9.4 × 10 5 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 IC 50 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.