Targeting of DNA molecules, BSA/c-Met tyrosine kinase receptors and anti-proliferative activity of bis(terpyridine)copper(ii) complexes

Abstract

A series of homoleptic bis(terpyridine)copper(ii) complexes of the type [Cu(L(1-5))2]Cl2 (), where L(1-5) = 4'-(4-substituted)-2,2':6',2''-terpyridines, have been synthesized and characterized. The molecular structure of complex was confirmed by the single crystal XRD technique, and the geometry of the complexes is best described as distorted octahedral. Structural parameters from the crystallographic and DFT studies are in good agreement with each other. The small HOMO-LUMO energy gap supports bioefficacy of the complexes. DNA binding studies show high intrinsic binding constant values 1.53 ± 0.15, 1.62 ± 0.08 and 3.09 ± 0.12 × 10(5) M(-1) for complexes , and , respectively, with intercalative mode of binding to CT-DNA. The binding results were further supported by molecular docking studies. The experimental results indicate that the interaction between the complexes and BSA protein involves a static quenching mechanism. The molecular docking studies with c-Met tyrosine kinase receptors show hydrophobic and π-π interactions. All the complexes bring about hydroxyl radical mediated DNA cleavage in the presence of H2O2. In vitro cytotoxicities of the complexes () were tested against three cancerous cell lines, namely human breast adenocarcinoma (MCF-7), epithelioma (Hep-2) and cervical (HeLa) cell lines, and one non-tumorigenic human dermal fibroblast (NHDF) cell line by MTT reduction assay. The morphological assessment data obtained using Hoechst 33258 staining revealed that complex induces apoptosis much more effectively than the other complexes.

Bis(thiosemicarbazone)copper(I) Complexes as Prospective Therapeutic Agents: Interaction with DNA/BSA Molecules, and In Vitro and In Vivo Anti‐Proliferative Activities

“…[48,49] Interestingly, the obtained values of binding constant of the complexes are higher than that reported for other copper(I) complexes, [50][51][52] thiosemicarbazone-based copper(II) complexes [53,54] and effective anticancer drug cisplatin (3.20 AE 0.15 3 10 4 M -1 ), but lesser than the classical intercalator (EB) in which the binding constants are in the order of 10 6 -10 7 M -1 . [55,56] The increased DT m (7.7-10.2 8C) values in the thermal denaturation studies also confirms the intercalative mode of binding ( Figure 2). Further, the fluorescence technique was also conducted to understand the type of interaction of complexes with CTÀDNA, in which the fluorescence intensity gradually decreased indicating the intercalative binding (Figures 2, S19 & S20).…”

“…The complexes show π−π stacking interaction of thiosemicarbazone ligands with base pairs (adenine & guanine), in which the distances from the centroid of intercalative ligand to the planes of neighboring base pairs are ∼3.6 Å (witness the Supporting Information for details). These docking observations also demonstrated the binding of complexes with CT−DNA through intercalative mode …”

Unusual coordination mode of aroyl/acyl thiourea ligands and their π‐arene ruthenium (II) piano‐stool complexes: Synthesis, molecular geometry, theoretical studies and biological applications

“…Generally a molecule having a small energy gap is more polarized and is known as soft molecule. The observed small energy gap indicates that the charge transfer easily occurs in it, which influences the more biological activity of the molecule …”

Synthesis, Characterization, Antimicrobial and Anticancer Activities of 14-Membered Macrocyclic Schiff Base Metal Complexes

“…Knoevenagel condensation between aldehyde and β-diketone act as dicarbonyls and fruitful source of macrocyclic polyaza ligand systems. Among the various β-diketones, curcumin is a versatile compound as their traditional consequence in medicinal field [10][11][12][13][14][15][16][17]. A search through literature reveals that more have been posted on the studies of Schiff bases [18][19][20].…”