Ternary Copper (II) complex based chemical probes for DNA targeting: Cytotoxic activity under visible light

Abstract

Among the bio‐metals, copper derivatives of O, N, S donor salicylaldehyde thiosemicarbazones have been obtained large interest due to their potential biological applications. Multisubstituted thiosemicarbazone ligand HL derived, new ternary Cu (II) complexes of [Cu(L)(bpy)] (1) and [Cu(L)(phen)] (2) (where, bpy is 2,2′‐bipyridine and phen is 1,10‐phenanthroline) have been synthesized and characterized using different physico‐chemical techniques. Complexes 1 and 2 are structurally characterized by single crystal X‐ray diffraction analysis, which reveals the trigonal bipyramidal distorted square based pyramid geometry of both the complexes 1 and 2 with ONS‐donor thiosemicarbazone bonded at the upper plane. The ground state electronic structures of complexes 1 and 2 have been investigated by using DFT/B3LYP theoretical evaluation with 6‐31G (d,p) and LANL2DZ basis set. The affinity towards DNA and human serum albumin has been evaluated using computational docking analysis and complex 2 exposes significant binding ability towards DNA and human serum albumin, because of its immense hydrophobicity. Consequently, complex 2 have higher antimicrobial in addition to the cytotoxic activity than complex 1 and free ligand HL under visible light. Along with, their apoptosis pathway of cytotoxicity has been evaluated by fluorescent microscopic analysis using acridine orange/ethidium bromide (AO/EB) stains. From these preliminary investigations, we believe that complex 2 can play a role as a more robust pharmacological agent.

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

“…It is important to note here that the results observed for 1 may be compared to many other reported DNA-binding copper complexes. 55 − 61 For example, the synthesized tyrosine Schiff base copper complexes by Reddy and Shilpa 55 showed good binding propensity for CT-DNA (3.01–3.47 × 10 4 M –1 ) and exhibited high nuclease activity as evident from the high hydrolytic DNA-cleavage rate constant (2.80–2.11 h –1 ) that amounts to a significant rate enhancement (0.5 to 0.7 × 10 8 fold) in comparison to non-catalyzed DNA hydrolysis. Yu et al 56 have reported four Cu(II) complexes of a reduced Schiff base ligand having diamine co-ligands that bind to DNA by intercalative mode and effectively induced apoptosis in cancer cells (A549, BGC823, and SGC7901), which was accompanied with increase in p53 and Bax and decrease in bcl2 expression.…”

In vitro biomolecular interaction studies and cytotoxic activities of copper(II) and zinc(II) complexes bearing ONS donor thiosemicarbazones

“…This provides evidence for the coordination of thiolato sulfur through iminolization after deprotonation. [ 28 ]…”

Synthesis of Copper and Cobalt complexes with a Hydrothermal Method and Their Applications in Antibiological Activity

“…At the same time, it is also involved in a variety of metabolic pathways, such as mitochondrial respiration, free radical scavenging and iron absorption [20,21] . Its toxicity is based on the direct production of reactive oxygen species (ROS) that cleave DNA and RNA, and its distribution and homeostasis can be highly regulated [22,23] . Studies suggest that copper is an essential cofactor for tumor angiogenesis, because most tumor growth and metastasis depend on angiogenesis, and angiogenesis requires a specific amount of copper [24–26] .…”

“…[20,21] Its toxicity is based on the direct production of reactive oxygen species (ROS) that cleave DNA and RNA, and its distribution and homeostasis can be highly regulated. [22,23] Studies suggest that copper is an essential cofactor for tumor angiogenesis, because most tumor growth and metastasis depend on angiogenesis, and angiogenesis requires a specific amount of copper. [24][25][26] Cobalt usually exists in the form of Co 2 + or Co 3 + , which can regulate the redox potential between normoxic and hypoxic tissues, and is the only d 7 ion.…”