C. Shobha Devi

Antiangiogenic Activity of Mononuclear Copper(II) Polypyridyl Complexes for the Treatment of Cancers

A series of four new mononuclear copper(II) polypyridyl complexes (1-4) have been designed, developed, and thoroughly characterized by several physicochemical techniques. The CT-DNA binding properties of 1-4 have been investigated by absorption, emission spectroscopy, and viscosity measurements. All the complexes especially 1 and 4 exhibit cytotoxicity toward several cancer cell lines, suggesting their anticancer properties as observed by several in vitro assays. Additionally, the complexes show inhibition of endothelial cell (HUVECs) proliferation, indicating their antiangiogenic nature. In vivo chick embryo angiogenesis assay again confirms the antiangiogenic properties of 1 and 4. The formation of excessive intracellular ROS (H2O2 and O2(•-)) and upregulation of BAX induced by copper(II) complexes may be the plausible mechanisms behind their anticancer activities. The present study may offer a basis for the development of new transition metal complexes through suitable choice of ligands for cancer therapeutics by controlling tumor angiogenesis.

Review: Synthesis, characterization, and DNA-binding properties of Ru(II) molecular “light switch” complexes

This article presents recent progress in our laboratory on the interactions of Ru(II) polypyridyl complexes with calf thymus DNA (CT-DNA). Mixed polypyridyl Ru(II) complexes [Ru(L)4(AIP)]2+ and [Ru(L)4PyIP]2+, where L is 4-amino pyridine and pyridine (AIP = 2-(9-anthryl)-1H-imidazo[4,5-f][1,10]phenanthroline; PyIP = 2-(1-pyrenyl)-1H-imidazo[4,5-f][1,10]phenanthroline), have been synthesized and characterized by elemental analysis, and physicochemical methods such as ESI-MS, UV-Vis, IR, and NMR spectroscopic techniques. Electronic absorption titrations, fluorescence spectroscopy, viscosity measurements, and salt-dependent studies of CT-DNA in the presence of incremental amounts of all four Ru(II) complexes clearly demonstrate that all four complexes bind to DNA by intercalation. The DNA-binding affinities of these complexes follow the order [Ru(4-APy)4(PyIP)]2+ > [Ru(Py)4PyIP]2+ > [Ru(4-APy)4(AIP)]2+ > [Ru(Py)4AIP]2+. Irradiation of pBR 322 DNA with these complexes results in nicking of the plasmid DNA. All four complexes were screened for antimicrobial activity. All complexes also exhibited DNA “light switch” properties. These results suggest that both ancillary ligand and intercalative ligand influence the binding of these complexes to DNA.

Cellular uptake, cytotoxicity, apoptosis and DNA-binding investigations of Ru(II) complexes.

Three new compounds, [Ru(Hdpa)2PyIP](ClO4)2·2H2O (1) [Ru(Hdpa)2FyIP](ClO4)2·2H2O (2) and [Ru(Hdpa)2IIP](ClO4)2·2H2O (3) have been synthesized and characterized by spectroscopic techniques such as elemental analysis, UV/Vis, FT-IR, (1)H NMR, (13)C NMR and mass spectra. The CT-DNA binding properties of 1-3 have been investigated by absorption, emission spectroscopy and viscosity measurements. Experimental results suggested that they can interact with DNA through intercalative mode with different binding strengths. These were found to promote the cleavage of plasmid DNA. Cell viability results indicated that all compounds showed significant dose dependent cytotoxicity in selected cell lines and 1 shown higher cytotoxicity than cisplatin on HeLa cells. Cellular uptake studies were studied by flow cytometry and confocal microscopy.

Ruthenium(II) ethylenediamine complexes with dipyridophenazine ligands: synthesis, characterization, DNA interactions, and antiproliferative activities

Ruthenium(II) complexes, [Ru(en)2dppz]2+ (1), [Ru(en)2qdppz]2+ (2), [Ru(en)2acdppz]2+ (3), and [Ru(en)2actatp]2+ (4), have been synthesized and characterized by IR, 1H, 13C-NMR and LC–MS. The interactions of these complexes with calf thymus (CT) DNA have been investigated by absorption, emission, viscosity, thermal denaturation, and circular dichroism. These techniques reveal that the complexes bind strongly to DNA. The apparent binding constants for the complexes decrease from 1 to 4 and are in the order of 8.5 ± 0.2 × 105 M−1 (1), 7.3 ± 0.8 × 105 M−1 (2), 4.3 ± 0.3 × 105 M−1 (3), and 7.5 ± 0.5 × 104 M−1 (4). The plot of log K versus log [Na+] yield slopes of −1.47, −1.44, −1.36, and −1.24 for 1, 2, 3, and 4, respectively. These complexes promote the photocleavage of pBR322 DNA. Cytotoxicities of these complexes suggest their possible anticancer activity.

Synthesis, Characterisation, Interaction with DNA, Cytotoxicity, and Apoptotic Studies of Ruthenium(II) Polypyridyl Complexes

We report the synthesis and characterisation of two new ruthenium(ii) polypyridyl complexes containing monodentate ancillary ligands [Ru(L)4(4HEPIP)], where L = 4-aminopyridine (1) or pyridine (2) and 4HEPIP = 2-(4-hydroxy-3-ethoxyphenyl)-1H-imidazo[4,5-f][1,10](phenanthroline). These complexes were characterised by elemental analysis and ultraviolet-visible, infrared, and 1H NMR spectroscopy. The binding properties of the two complexes towards calf thymus (CT)-DNA were investigated with different spectrophotometric methods, viscosity measurements, and salt dependent studies. Experimental results indicated that the complexes interact with CT-DNA base pairs by intercalation. Upon irradiation at 365 nm, these complexes efficiently cleave pBR322 DNA from super coiled form I to nicked form II. Their cytotoxicity on different cancer cell lines such as A549, Du145, and HeLa was investigated. The IC50 values are 39.5, 28.3, and 27.3 μM for complex 1, and 55, 67.9, and 47.9 μM for complex 2 respectively. Cellular uptake and apoptosis induced by these complexes was also studied.

Correlation Between Molecular Modelling and Spectroscopic Techniques in Investigation With DNA Binding Interaction of Ruthenium(II) Complexes.

The DNA binding studies of rutheniumu(II) polypyridyl complexes {[Ru(phen)2Mipc]2+, [Ru(bpy)2Mipc]2+, [Ru(dmb)2Mipc]2+, [Ru(phen)2BrIPC]2+, [Ru(bpy)2BrIPC]2+, [Ru(dmb)2BrIPC]2+, [Ru(phen)2PIP-Cl]2+, [Ru(bpy)2PIP-Cl]2+, [Ru(dmb)2PIP-Cl]2+, [Ru(phen)2IPPBA]2+, [Ru(bpy)2IPPBA]2+, [Ru(dmb)2IPPBA]2+} with DNA investigated by electronic absorption titration, emission and molecular modelling studies to identify the binding interactions. All these complexes are showing good binding constant values ~104 to 105. The intercalative ligands makes the binding of the ruthenium(II) complex with DNA as intercalation mode. The ancillary ligands 1,10-phenanthroline (phen), 4,4′-Dimethyl-2,2′-dipyridyl (dmb) and 2,2′-dipyridine (bpy) having been discovered found to be involved in bond formation with the phosphate backbone of nucleotide base pairs in ruthenium(II) complex–DNA docked complex. The molecular docking results are good agreement with experimental results. The molecular modelling technic should help to extend knowledge about the nature (or) mode of binding of these ruthenium(II) complexes with (calf thymus) CT-DNA.

Recent Advances in Copper Intercalators as Anticancer Agents

AbstractCopper is a part of various enzymes and helps them to function properly. It can be effectively used to produce promising anticancer drugs and presently, many studies are being pursued worldwide on the development of copper-based complexes as potential anticancer drugs. Herein, we briefly discuss the importance of reactive oxygen species in biological applications and copper(II) complexes as anticancer drugs. The anti-angiogenic properties of mono-nuclear copper(II) complexes have been demonstrated by in vivo chick embryo angiogenesis analysis. The plausible mechanism behind anticancer activity of these complexes is by the formation of excessive intracellular Reactive Oxygen Species (ROS). ROS is a composite term used for oxygen derivative non-radicals and free radicals of highly reactive components, that enhances the killing response of immune cells to microbial invasion. Previous reports have shown that ROS plays an important role as a messenger in cell cycling and normal cell signal transduction. Graphical AbstractThe generation of singlet oxygen and healing the tumor cells with singlet oxygen in presence of UV-light.

Analytical Techniques Used to Detect DNA Binding Modes of Ruthenium(II) Complexes with Extended Phenanthroline Ring

This review describes the analytical techniques used to detect DNA-probes such as Ru(II) complexes with hetero cyclic imidazo phenanthroline (IP) ligands. Studies on drug-DNA interactions are useful biochemical techniques for visualization of DNA both in vitro and in vivo. The interactions of small molecules that binds to DNA are mainly classified into two major classes, one involving covalent binding and another non-covalent binding. Covalent binding in DNA can be irreversible and may leads to inhibition of all DNA processes which subsequently leads to cell death. Usually, covalent interactions leads to permanent changes in the structure of nucleic acids. The non-covalent interaction of molecules with DNA can be due to electrostatic interaction, intercalation and groove binding. These interactions of DNA probes can be explored by various spectroscopic techniques viz. UV–visible, emission, emission quenching spectroscopy, viscosity and thermal denaturation measurements.