Chiral nano heterobimetallic DNA receptors: In vitro binding studies, cleavage activity and DNA condensation studies (TEM and AFM imaging) (original) (raw)
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2013
Understanding the interaction of pharmaceutical agents to DNA is essential for underlying their mode of action, site, sequence and structural specificity of their binding reactions. Chirality of a complex is a pre–requisite criterion for an appropriate model drug design, since usually two enantiomers of the same metal complex have different binding constants and recognition properties. Interaction between small molecules and DNA provides a structural guideline in rational therapeutic drug design regime and to understand the mechanism of action of DNA–targeted drugs. We have described briefly the overview of chiral late 3d–transition metal–based (Co(II), Cu(II) and Zn(II)) chemotherapeutic agents which show enantioselective and preferential binding to inherently chiral DNA molecule.
Interaction of chromium(III) complex of chiral binaphthyl tetradentate ligand with DNA
Bioorganic & Medicinal Chemistry, 2006
Since conformation of the molecule plays a vital role in the activity of drug, we have investigated the DNA interaction of a chromium(III) complex with ligands in two conformations. Chromium(III) complexes derived from chiral binaphthyl Schiff base ligands, viz. R-and S-2,2 0-bis(salicylideneamino) 1,1 0-binaphthyl, have been synthesized and characterized by mass, IR, and electronic spectra. The interaction of these R-and S-binaphthyl Schiff base chromium(III) complexes with CT-DNA was investigated with the goal of examining whether the chirality has an influence on the chromium(III)-DNA binding properties. The difference in chirality of the ligand did not show any striking difference in binding properties. The binding constants for R and S conformers were estimated to be 18 (±0.4) • 10 3 and 9.4 (±0.3) • 10 3 M À1 , respectively, through spectroscopic titrations. All the experimental results are suggestive that both the isomers are DNA groove binders. The results of steady-state as well as time-resolved fluorescence experiments, however, suggest that the R conformer has restricted mobility when bound to DNA because it is more deeply buried in the groove of DNA compared to the S isomer.
Chemistry & Biodiversity, 2006
The new chiral macrocyclic complexes [1,2-bis(1H-benzimidazol-2-yl)-1-(1,8-dihydro-1,3,5,8,10,12hexaazacyclotetradecane)-2-hydroxyethanolate] copper(II) and-nickel(II) perchlorate, 3 and 4, respectively, were synthesized by the reaction of 1,2-bis(1H-benzimidazol-2-yl)ethane-1,2-diol (L) and (1,8-dihydro-1,3,5,8,10,12-hexaazacyclotetradecane)copper(II) and-nickel(II) diperchlorate complexes, 1 and 2, respectively. All complexes were characterized by various spectroscopic techniques. Molarconductance measurements showed that all of the complexes are ionic in nature. In complexes 3 and 4, the metal center is encapsulated by the ligand L in a pentacoordinated environment. The optical-rotation values ([a] D) of 3 and 4 at 258 indicate that the complexes are chiral. Absorption-and fluorescencespectral studies, cyclic voltammetry, and viscosity measurements have been carried out to assess the comparative binding of complexes 1 and 3 with calf thymus (CT)-DNA. Analysis of the results suggests that the new chiral complex 3 binds to CT-DNA through a partial intercalation mode that is different from the binding mode of parent achiral complex 1. The complexes 1 and 3 bind to CT-DNA with binding constants K b of 2.7 Â 10 4 and 6.6 Â 10 4 m À 1 , respectively. Circular-dichroism (CD) studies have been further employed to ascertain the binding mode of complex 3, which is consistent with the other spectral studies.
2015
A novel macroacyclic N 2O2 based Schiff base ligand (L), obtained by the cond ensation of 9,10-phenanthrenequinone and 1,8-diaminonaphthalene, has been used to synthe size the mononuclear complexes of the type [M(L)]Cl 2 [M= Co(II), Ni(II), Cu(II) and Zn(II)]. The newly synth esized ligand (L) and its complexes have been chara terized with the help of elemental analyses, conductance measure ments, electronic, C-NMR, infrared and mass spectral studies. The formation of macroacyclic framework ha s been inferred from the appearance of imine (C=N) and (MN) band in IR spectra and the signal observed in C-NMR spectra. The stoichiometry and the nature of the complexes have been deduced from the results of ele mental analyses and conductance data. The structura l distortion in Cu(II) complex has been deduced on EP R data. The electrochemical behaviour of the Cu(II) complex has been studied by cyclic voltammetry. Absorption, Fluorescence, circular dichroism and viscosity mea surement studies...
Chiral heterobimetallic complexes targeting human DNA-topoisomerase Iα
Dalton Transactions, 2013
The chiral monometallic Cu II (1) and Zn II (2) and heterobimetallic Cu II-Sn IV and Zn II-Sn IV complexes with tridentate chiral Schiff base-ONO-ligand in the presence of nitrogen donor heterocyclic ligand imidazole; were prepared and characterized by various physico-chemical and spectroscopic methods. Preliminary complex-DNA interaction studies employing optical methods revealed that 3 displayed a higher propensity towards the drug target DNA double helix and recommended predominantly an electrostatic mode of interaction as well as a groove binding affinity of the complex with CT-DNA. This was quantified by K b and K SV values of complexes 1-4, which demonstrated a multifold increase in complex 3 binding to CT DNA and clearly demonstrates its potency to act as a chemotherapeutic agent. Furthermore, the gel electrophoretic patterns of supercoiled pBR322 DNA with varying concentrations of complex 3 exhibits the ability to cleave DNA and follow a freely diffusible radical mechanism. The antiproliferative effects of complex 3 on human hepatoma cancer cells (Huh7) was investigated. Human Topo I inhibition assay by complex 3 was performed and results confirmed significantly good activity at lower concentrations than some of the classical Topo I inhibitors. Additionally, complex 3 was investigated for the expression of MMP-2 and TGF-β by real time PCR. The cellular uptake of complex 3 by HeLa cells was studied by confocal microscopy.
Journal of Photochemistry and Photobiology B: Biology, 2011
New Schiff base ligand L derived from the condensation reaction of 2-amino-3-formylchromone with (R)-2-amino-2-phenylethanol was synthesized and characterized which involves combination element of ammine functionality and naturally occurring heterocyclic chromone, 4H-benzopyran-4-one. Subsequently, their complexes 1 and 2 with Cu(NO 3 ) 2 and Zn(NO 3 ) 2 , respectively were prepared. The DNA binding studies of the ligand L and complexes 1 and 2 with CT-DNA as compared to classical anticancer drug cisplatin were carried out by employing different optical methods viz, UV-vis, fluorescence, circular dichroism and viscosity measurements. Furthermore, the absorption studies, 1 H and 31 P with mononucleotides were also monitored to examine the base specific interactions of the transition metal complexes which revealed a higher propensity of copper(II) complex 1 for 5 0 -GMP while for zinc(II) complex 2 towards 5 0 -TMP involving groove binding mechanism of the complexes towards DNA. The complex 1 exhibits a remarkable DNA cleavage activity with pBR322 DNA in presence of different activators and cleavage reaction involves various oxygen species suggesting the involvement of active oxygen species for the DNA scission.
Nucleosides, Nucleotides and Nucleic Acids, 2019
Three new cobalt(III) polypyridyl complexes, [Co(L-L) 2 IIP] 3þ where IIP = 2-(2H-isoindol-1-yl)-2H-imidazo[4,5-f][1, 10]phenanthroline, L ¼ 1) phen (1,10-phenanthroline), 2) bpy (2,2'bipyridyl), 3) dmb (4, 4-dimethyl 2, 2'-bipyridine) have been synthesized, characterized (UV-VIS, IR, 1 HNMR and 13 C NMR spectroscopy) and screened for their in vitro antibacterial activity against E.coli, Staphylococcus aureus and Bacillus subtilis. The binding of these complexes with calf-thymus DNA (CT-DNA) has been investigated by absorption and fluorescence spectroscopy, viscosity measurements. The experimental studies indicate that complexes bind to CT-DNA by means of intercalation, but with different binding affinities due to differences in the planarity of the ancillary ligand. The complexes promote photocleavage of plasmid DNA from super coiled form I to the open circular form II. The antibacterial activities suggest that the metal complexes are more active as compared to the prepared un-complexed IIP ligand. In addition, a conformational search was carried out by Molecular Dynamics Simulations, and docking revealed that complexes intercalate between base pairs of DNA. The experimental and computational approaches reveal that the length of the intercalator and the nature of ancillary ligand are highly important factors for DNA binding.
Transition Metal Chemistry, 2008
A new series of 14-membered pendant arm hexaazamacrocyclic complexes of the type [MLX2] · [M = Co(II), Ni(II), Cu(II) or Zn(II) for X = Cl; Co(II), Ni(II), Cu(II) or Zn(II) for X = NO3] has been synthesized by metal template condensation of 1,2-phenylenediamine and 1,4-phenylenediamine with formaldehyde in methanol. The mode of bonding and overall geometry of these complexes have been deduced by elemental analyses, molar conductance values, FT-IR, 1H-NMR, 13C-NMR, EPR, ESI-mass and UV–VIS along with magnetic measurement studies. The fluorescence and UV–VIS studies revealed a significant binding ability to DNA.