Synthesis, Characterization, Crystal Structure, DNA and HSA Interactions, and Anticancer Activity of a Mononuclear Cu(II) Complex with a Schiff Base Ligand Containing a Thiadiazoline Moiety

Abstract

A mononuclear Cu­(II) complex [Cu­(HL)­(o-phen)]·H2O (1) [H3L =, o-phen = 1,10-phenanthroline] was isolated from methanol, and its X-ray single-crystal structure was determined. Frozen glass X-band EPR of 1 in dimethylformamide (DMF) at LNT showed a spectrum that is characteristic of a monomeric tetragonal character with g ∥ = 2.164, g ⊥ = 2.087, A ∥ = 19.08 mT, and A ⊥ ≤ 4 mT. Electronic spectroscopic studies using calf thymus DNA (CT-DNA) showed strong binding affinity of 1 as reflected from its intrinsic binding constant (K b) value of 2.85 × 105 M–1. Competitive behavior of 1 with ethidium bromide (EB) displayed intercalative binding of DNA (K app = 1.3 × 106 M–1). The compound displayed significant oxidative cleavage of pUC19 DNA. The interaction between HSA and complex 1 was examined by employing fluorescence and electronic absorption spectroscopic experiments. The secondary and tertiary structures of HSA were found to be altered as suggested by three-dimensional (3D) fluorescence experiments. The affinity of 1 to bind to HSA was found to be strong as indicated from its value of the binding constant (K a = 2.89 × 105 M–1). Intrinsic fluorescence of the protein was found to be reduced through a mechanism of static quenching as suggested from the k q (2.01 × 1013 M–1 s–1) value, the bimolecular quenching constant. The Förster resonance energy transfer (FRET) process may also be accounted for such a high k q value. The r value (2.85 nm) calculated from FRET theory suggested that the distance between complex 1 (acceptor) and HSA (donor) is quite close. Complex 1 primarily bound to HSA in subdomain IIA as suggested by molecular docking studies. IC50 values (0.80 and 0.43 μM, respectively) obtained from the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay with HeLa and MCF7 cells suggested remarkable in vitro anticancer activity of 1. Nuclear dual staining assays revealed that cell death occurred via apoptosis in HeLa cells and reactive oxygen species (ROS) accumulation caused apoptosis induction. On treatment with a 5 μM dose of 1 in HeLa cells, the cell population significantly increased in the G2/M phase, while it was decreased in G0/G1 and S phases as compared to the control, clearly indicating G2/M phase arrest.

Mixed Ligand Mononuclear Copper(II) Complex as a Promising Anticancer Agent: Interaction Studies with DNA/HSA, Molecular Docking, and In Vitro Cytotoxicity Studies

“…Flow cytometry was used to analyze the PI-stained cell population in different cell cycle stages. , A typical cell cycle consists of four phases, that is, G1, S, G2, and M. Exposure of HeLa cells to complex 1 led to an increase in the cell population in the S phase, wherein DNA gets replicated. This population increase was prominent, and a dose-dependent increase with complex 1 concentration was observed.…”

Ruthenium Complexes as Potential Cancer Cell Growth Inhibitors for Targeted Chemotherapy

“…The DNA affinities of the compounds are evaluated using absorbance titration studies, [57] and it is proposed that the complexes’ DNA binding is due to the intercalative mode, which is further investigated using EB quenching assays [58] . Using agarose gel electrophoresis and a 365 nm exposure, we investigated photoinduced DNA cleavage [59] .…”

Sparfloxacin – Cu(ii) – aromatic heterocyclic complexes: synthesis, characterization and in vitro anticancer evaluation

“…These results indicated that the complexes could interact with CT-DNA. [26][27][28] The different binding forces were due to the difference of the N^N ligands, in which the NH group of HPB is more helpful for the interaction between complex 1 and DNA.…”