Water-soluble DNA minor groove binders as potential chemotherapeutic agents: synthesis, characterization, DNA binding and cleavage, antioxidation, cytotoxicity and HSA interactions

Abstract

Two new water-soluble copper(ii)-dipeptide complexes: [Cu(glygly)(PyTA)]ClO4·1.5H2O (1) and [Cu(glygly)(PzTA)]ClO4·1.5H2O (2) (glygly = glycylglycine anion, PyTA = 2,4-diamino-6-(2'-pyridyl)-1,3,5-triazine and PzTA = 2,4-diamino-6-(2'-pyrazino)-1,3,5-triazine), utilizing two interrelated DNA base-like ligands (PyTA and PzTA), have been synthesized and characterized. The structure elucidation for 1 performed by single crystal X-ray diffraction showed a one dimensional chain conformation in which the central copper ions arrange in a five-coordinate distorted square-pyramidal geometry. Spectroscopic titration, viscosity and electrophoresis measurements revealed that the complexes bound to DNA via an outside groove binding mode, and cleaved pBR322 DNA efficiently in the presence of ascorbate, probably via an oxidative mechanism with the involvement of ˙OH and ˙O2(-). Notably, the complexes exhibited considerable in vitro cytotoxicity against four human carcinoma cell lines (HepG2, HeLa, A549 and U87) with IC50 values ranging from 41.68 to 159.17 μM, in addition to their excellent SOD mimics (IC50 ~ 0.091 and 0.114 μM). Besides, multispectroscopic evidence suggested their HSA-binding at the cavity containing Trp-214 in subdomain IIA with moderate affinity, mainly via hydrophobic interaction. Further, the molecular docking technique utilized for ascertaining the mechanism and mode of action towards DNA and HSA theoretically verified the experimental results.

Groove binding mediated structural modulation and DNA cleavage by quinoline appended chalcone derivative

“…where F 0 , F, K sv, k q , τ and s -1 ) also supports the static quenching behavior [33][34][35] of the fluorophore by the nucleic acid.…”

Synthesis, crystal structures and DNA/human serum albumin binding of ternary Cu(II) complexes containing amino acids and 6‐(pyrazin‐2‐yl)‐1,3,5‐triazine‐2,4‐diamino

“…To assess the binding ability between the complexes and CT‐DNA, the intrinsic binding constants ( K b ) can be calculated using the following equation: where [DNA] is the concentration of CT‐DNA, and ε a , ε f and ε b correspond to A obsd /[complex], absorption coefficient of the free compound and absorption coefficient of the compound when fully bound to DNA, respectively. From plots of [DNA]/( ε a − ε f ) versus [DNA], the K b values were found to be 4.71 × 10 3 M −1 for 1 and 1.98 × 10 3 M −1 for 2 , which are close to that of the reported groove binder Cu(II)–dipeptide complex with the pzta ligand ( K b = 6.04 × 10 3 M −1 ) . The binding affinity of complex 1 towards DNA is stronger than that of 2 , which may be related to the hydrophobic side chain of l ‐valine.…”

Exploring the copper(II)–aminotriazole complex-binding sites of human serum albumin

“…It clearly indicates that the fluorescence intensity of HSA decreases regularly with increasing concentration of Cu(II)-ATA, which confirms some interactions between the complex and HSA and alteration of the local microenvironment around the Trp-214 residue in HSA. No prominent red shift or hypsochromic shift was observed, suggesting no conformational change of the tertiary structure of HSA [17].…”