Benzothiazole hydrazones of furylbenzamides preferentially stabilize c-MYC and c-KIT1 promoter G-quadruplex DNAs

摘要: The stabilization of G-quadruplex DNA structures by using small molecule ligands having simple structural scaffolds has the potential to be harnessed for developing next generation anticancer agents. Because diversity G-quadruplexes, it is challenging design stabilizing ligands, which can specifically bind a particular quadruplex topology. To address this, herein, we report and synthesis three benzothiazole hydrazones furylbenzamides different side chains (ligands 1, 2 3), show preferential promoter DNAs (c-MYC c-KIT1) parallel topologies over telomeric duplex DNAs. CD melting study revealed that all in ligand 2, exhibit higher toward quadruplexes (ΔTm = 10–15 °C) as compared antiparallel (h-RAS1), 0–3 °C). FID assay fluorimetric titration results also reveal binding c-MYC c-KIT1 Validating these further, Taq polymerase stop showed IC50 ∼ 6.4 μM with template, whereas same template was found >200 μM. Molecular modeling dynamics studies demonstrated 1 : 1 stoichiometry stacking electrostatic interactions play important roles structure. Taken together, presented here provide new insights into structurally